The process by which a DNA molecule is duplicated.
Deoxyribonucleic acid that makes up the genetic material of viruses.
A unique DNA sequence of a replicon at which DNA REPLICATION is initiated and proceeds bidirectionally or unidirectionally. It contains the sites where the first separation of the complementary strands occurs, a primer RNA is synthesized, and the switch from primer RNA to DNA synthesis takes place. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The temporal order in which the DNA of the GENOME is replicated.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Proteins found in any species of virus.
Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Established cell cultures that have the potential to propagate indefinitely.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The origin recognition complex is a multi-subunit DNA-binding protein that initiates DNA REPLICATION in eukaryotes.
DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.
A DNA-binding protein that consists of 5 polypeptides and plays an essential role in DNA REPLICATION in eukaryotes. It binds DNA PRIMER-template junctions and recruits PROLIFERATING CELL NUCLEAR ANTIGEN and DNA POLYMERASES to the site of DNA synthesis.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Any DNA sequence capable of independent replication or a molecule that possesses a REPLICATION ORIGIN and which is therefore potentially capable of being replicated in a suitable cell. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
A single-stranded DNA-dependent RNA polymerase that functions to initiate, or prime, DNA synthesis by synthesizing oligoribonucleotide primers. EC 2.7.7.-.
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
Ribonucleic acid that makes up the genetic material of viruses.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Deoxyribonucleic acid that makes up the genetic material of fungi.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The complete genetic complement contained in a DNA or RNA molecule in a virus.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It contains a NUCLEAR LOCALIZATION SIGNAL which may provide targeting of the protein complex and an extended N-terminus which is rich in SERINE residues.
A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms but may be present in higher organisms. Use also for a more complex form of DNA polymerase III designated as DNA polymerase III* or pol III* which is 15 times more active biologically than DNA polymerase I in the synthesis of DNA. This polymerase has both 3'-5' and 5'-3' exonuclease activities, is inhibited by sulfhydryl reagents, and has the same template-primer dependence as pol II. EC
A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. EC
A DNA-dependent DNA polymerase characterized in prokaryotes and may be present in higher organisms. It has both 3'-5' and 5'-3' exonuclease activity, but cannot use native double-stranded DNA as template-primer. It is not inhibited by sulfhydryl reagents and is active in both DNA synthesis and repair. EC
The functional hereditary units of VIRUSES.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Geminin inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex. It is absent during G1 phase of the CELL CYCLE and accumulates through S, G2,and M phases. It is degraded at the metaphase-anaphase transition by the ANAPHASE-PROMOTING COMPLEX-CYCLOSOME.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It is also found in tightly-bound trimeric complex with MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 4 and MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 6.
Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.
Proteins found in any species of bacterium.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Structures within the nucleus of bacterial cells consisting of or containing DNA, which carry genetic information essential to the cell.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
A family of proteins that were originally identified in SACCHAROMYCES CEREVISIAE as being essential for maintaining the structure of minichromosomes00. They form into a protein complex that has helicase activity and is involved in a variety of DNA-related functions including replication elongation, RNA transcription, chromatin remodeling, and genome stability.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It contains a NUCLEAR LOCALIZATION SIGNAL, which provide targeting of the protein complex. In addition, acetylation of this protein may play a role in regulating of DNA replication and cell cycle progression.
A genus of potentially oncogenic viruses of the family POLYOMAVIRIDAE. These viruses are normally present in their natural hosts as latent infections. The virus is oncogenic in hosts different from the species of origin.
The rate dynamics in chemical or physical systems.
Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A family of DNA helicases that participate in DNA REPLICATION. They assemble into hexameric rings with a central channel and unwind DNA processively in the 5' to 3' direction. DnaB helicases are considered the primary replicative helicases for most prokaryotic organisms.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
Virulent bacteriophage and type species of the genus T4-like phages, in the family MYOVIRIDAE. It infects E. coli and is the best known of the T-even phages. Its virion contains linear double-stranded DNA, terminally redundant and circularly permuted.
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992)
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
Preparations of cell constituents or subcellular materials, isolates, or substances.
Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
Species of the genus MASTADENOVIRUS, causing a wide range of diseases in humans. Infections are mostly asymptomatic, but can be associated with diseases of the respiratory, ocular, and gastrointestinal systems. Serotypes (named with Arabic numbers) have been grouped into species designated Human adenovirus A-F.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.
A CELL LINE derived from the kidney of the African green (vervet) monkey, (CERCOPITHECUS AETHIOPS) used primarily in virus replication studies and plaque assays.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Enzymes that catalyze the template-directed incorporation of ribonucleotides into an RNA chain. EC 2.7.7.-.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It is also found in tightly-bound trimeric complex with MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 6 and MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 7.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
Proteins found in any species of fungus.
A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Proteins obtained from ESCHERICHIA COLI.
Proteins encoded by a VIRAL GENOME that are produced in the organisms they infect, but not packaged into the VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY.
Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
A genus of owlet moths of the family Noctuidae. These insects are used in molecular biology studies during all stages of their life cycle.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Viruses whose host is Escherichia coli.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Endonucleases that remove 5' DNA sequences from a DNA structure called a DNA flap. The DNA flap structure occurs in double-stranded DNA containing a single-stranded break where the 5' portion of the downstream strand is too long and overlaps the 3' end of the upstream strand. Flap endonucleases cleave the downstream strand of the overlap flap structure precisely after the first base-paired nucleotide, creating a ligatable nick.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A minichromosome maintenance protein that is a key component of the six member MCM protein complex. It is also found in tightly-bound trimeric complex with MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 4 and MINICHROMOSOME MAINTENANCE COMPLEX COMPONENT 7.
Deletion of sequences of nucleic acids from the genetic material of an individual.
Elements of limited time intervals, contributing to particular results or situations.
3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.
Compounds that inhibit cell production of DNA or RNA.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A series of 7 virulent phages which infect E. coli. The T-even phages T2, T4; (BACTERIOPHAGE T4), and T6, and the phage T5 are called "autonomously virulent" because they cause cessation of all bacterial metabolism on infection. Phages T1, T3; (BACTERIOPHAGE T3), and T7; (BACTERIOPHAGE T7) are called "dependent virulent" because they depend on continued bacterial metabolism during the lytic cycle. The T-even phages contain 5-hydroxymethylcytosine in place of ordinary cytosine in their DNA.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
The type species of the genus MICROVIRUS. A prototype of the small virulent DNA coliphages, it is composed of a single strand of supercoiled circular DNA, which on infection, is converted to a double-stranded replicative form by a host enzyme.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC (ATP) and EC (NAD).
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS.
The type species of PARVOVIRUS prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias.
The type species of SIMPLEXVIRUS causing most forms of non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in the dorsal root ganglion. It then is periodically reactivated throughout life causing mostly benign conditions.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
A genus of the family BACULOVIRIDAE, subfamily Eubaculovirinae, characterized by the formation of crystalline, polyhedral occlusion bodies in the host cell nucleus. The type species is Autographa californica nucleopolyhedrovirus.
A species of DELTAPAPILLOMAVIRUS infecting cattle.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.
DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.
The interactions between a host and a pathogen, usually resulting in disease.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
Viruses whose host is Bacillus. Frequently encountered Bacillus phages include bacteriophage phi 29 and bacteriophage phi 105.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.
Any method used for determining the location of and relative distances between genes on a chromosome.
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
An error-prone mechanism or set of functions for repairing damaged microbial DNA. SOS functions (a concept reputedly derived from the SOS of the international distress signal) are involved in DNA repair and mutagenesis, in cell division inhibition, in recovery of normal physiological conditions after DNA repair, and possibly in cell death when DNA damage is extensive.
The functional hereditary units of FUNGI.
Proteins prepared by recombinant DNA technology.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
Separation of particles according to density by employing a gradient of varying densities. At equilibrium each particle settles in the gradient at a point equal to its density. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals.
A temperate inducible phage and type species of the genus lambda-like viruses, in the family SIPHOVIRIDAE. Its natural host is E. coli K12. Its VIRION contains linear double-stranded DNA with single-stranded 12-base 5' sticky ends. The DNA circularizes on infection.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
A species of gram-positive bacteria that is a common soil and water saprophyte.
A family of plant viruses where the VIRION possesses an unusual morphology consisting of a pair of isometric particles. Transmission occurs via leafhoppers or whitefly. Some viruses cause economically important diseases in cultivated plants. There are four genera: Mastrevirus, Curtovirus, Topocuvirus, and BEGOMOVIRUS.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.
Transport proteins that carry specific substances in the blood or across cell membranes.
Method for measuring viral infectivity and multiplication in CULTURED CELLS. Clear lysed areas or plaques develop as the VIRAL PARTICLES are released from the infected cells during incubation. With some VIRUSES, the cells are killed by a cytopathic effect; with others, the infected cells are not killed but can be detected by their hemadsorptive ability. Sometimes the plaque cells contain VIRAL ANTIGENS which can be measured by IMMUNOFLUORESCENCE.
The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos.
An enzyme that catalyses RNA-template-directed extension of the 3'- end of an RNA strand by one nucleotide at a time, and can initiate a chain de novo. (Enzyme Nomenclature, 1992, p293)
A mature haploid female germ cell extruded from the OVARY at OVULATION.
An ATP-dependent exodeoxyribonuclease that cleaves in either the 5'- to 3'- or the 3'- to 5'-direction to yield 5'-phosphooligonucleotides. It is primarily found in BACTERIA.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
A species of gram-negative, aerobic bacteria that consist of slender vibroid cells.
Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities.
Deoxycytidine (dihydrogen phosphate). A deoxycytosine nucleotide containing one phosphate group esterified to the deoxyribose moiety in the 2'-,3'- or 5- positions.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.
Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
Either of the two longitudinally adjacent threads formed when a eukaryotic chromosome replicates prior to mitosis. The chromatids are held together at the centromere. Sister chromatids are derived from the same chromosome. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Structures within the nucleus of archaeal cells consisting of or containing DNA, which carry genetic information essential to the cell.
Plasmids encoding bacterial exotoxins (BACTERIOCINS).
Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-.
A cell line derived from cultured tumor cells.
Viruses whose hosts are bacterial cells.
A family of very small DNA viruses containing a single molecule of single-stranded DNA and consisting of two subfamilies: PARVOVIRINAE and DENSOVIRINAE. They infect both vertebrates and invertebrates.
The residual framework structure of the CELL NUCLEUS that maintains many of the overall architectural features of the cell nucleus including the nuclear lamina with NUCLEAR PORE complex structures, residual CELL NUCLEOLI and an extensive fibrogranular structure in the nuclear interior. (Advan. Enzyme Regul. 2002; 42:39-52)
The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
A genus of the family HERPESVIRIDAE, subfamily ALPHAHERPESVIRINAE, consisting of herpes simplex-like viruses. The type species is HERPESVIRUS 1, HUMAN.
Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)

Human topoisomerase I promotes initiation of simian virus 40 DNA replication in vitro. (1/17470)

Addition of purified human topoisomerase I (topo I) to simian virus 40 T antigen-driven in vitro DNA replication reactions performed with topo I-deficient extracts results in a greater than 10-fold stimulation of completed molecules as well as a more than 3-fold enhancement of overall DNA replication. To further characterize this stimulation, we first demonstrate that bovine topo I but not Escherichia coli topo I can also enhance DNA replication. By using several human topo I mutants, we show that a catalytically active form of topo I is required. To delineate whether topo I influences the initiation or the elongation step of replication, we performed delayed pulse, pulse-chase, and delayed pulse-chase experiments. The results illustrate that topo I cannot promote the completion of partially replicated molecules but is needed from the beginning of the reaction to initiate replication. Competitive inhibition experiments with the topo I binding T antigen fragment 1-246T and a catalytically inactive topo I mutant suggest that part of topo I's stimulation of replication is mediated through a direct interaction with T antigen. Collectively, our data indicate that topo I enhances the synthesis of fully replicated DNA molecules by forming essential interactions with T antigen and stimulating initiation.  (+info)

The 3'-->5' exonucleases of DNA polymerases delta and epsilon and the 5'-->3' exonuclease Exo1 have major roles in postreplication mutation avoidance in Saccharomyces cerevisiae. (2/17470)

Replication fidelity is controlled by DNA polymerase proofreading and postreplication mismatch repair. We have genetically characterized the roles of the 5'-->3' Exo1 and the 3'-->5' DNA polymerase exonucleases in mismatch repair in the yeast Saccharomyces cerevisiae by using various genetic backgrounds and highly sensitive mutation detection systems that are based on long and short homonucleotide runs. Genetic interactions were examined among DNA polymerase epsilon (pol2-4) and delta (pol3-01) mutants defective in 3'-->5' proofreading exonuclease, mutants defective in the 5'-->3' exonuclease Exo1, and mismatch repair mutants (msh2, msh3, or msh6). These three exonucleases play an important role in mutation avoidance. Surprisingly, the mutation rate in an exo1 pol3-01 mutant was comparable to that in an msh2 pol3-01 mutant, suggesting that they participate directly in postreplication mismatch repair as well as in other DNA metabolic processes.  (+info)

Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases. (3/17470)

Mitotic double-strand break (DSB)-induced gene conversion at MAT in Saccharomyces cerevisiae was analyzed molecularly in mutant strains thermosensitive for essential replication factors. The processivity cofactors PCNA and RFC are essential even to synthesize as little as 30 nucleotides following strand invasion. Both PCNA-associated DNA polymerases delta and epsilon are important for gene conversion, though a temperature-sensitive Pol epsilon mutant is more severe than one in Pol delta. Surprisingly, mutants of lagging strand replication, DNA polymerase alpha (pol1-17), DNA primase (pri2-1), and Rad27p (rad27 delta) also greatly inhibit completion of DSB repair, even in G1-arrested cells. We propose a novel model for DSB-induced gene conversion in which a strand invasion creates a modified replication fork, involving leading and lagging strand synthesis from the donor template. Replication is terminated by capture of the second end of the DSB.  (+info)

Tissue factor pathway inhibitor-2 is a novel mitogen for vascular smooth muscle cells. (4/17470)

A mitogen for growth-arrested cultured bovine aortic smooth muscle cells was purified to homogeneity from the supernatant of cultured human umbilical vein endothelial cells by heparin affinity chromatography and reverse-phase high performance liquid chromatography. This mitogen was revealed to be tissue factor pathway inhibitor-2 (TFPI-2), which is a Kunitz-type serine protease inhibitor. TFPI-2 was expressed in baby hamster kidney cells using a mammalian expression vector. Recombinant TFPI-2 (rTFPI-2) stimulated DNA synthesis and cell proliferation in a dose-dependent manner (1-500 nM). rTFPI-2 activated mitogen-activated protein kinase (MAPK) activity and stimulated early proto-oncogene c-fos mRNA expression in smooth muscle cells. MAPK, c-fos expression and the mitogenic activity were inhibited by a specific inhibitor of MAPK kinase, PD098059. Thus, the mitogenic function of rTFPI-2 is considered to be mediated through MAPK pathway. TFPI has been reported to exhibit antiproliferative action after vascular smooth muscle injury in addition to the ability to inhibit activation of the extrinsic coagulation cascade. However, structurally similar TFPI-2 was found to have a mitogenic activity for the smooth muscle cell.  (+info)

Regulation of the start of DNA replication in Schizosaccharomyces pombe. (5/17470)

Cells of Schizosaccharomyces pombe were grown in minimal medium with different nitrogen sources under steady-state conditions, with doubling times ranging from 2.5 to 14 hours. Flow cytometry and fluorescence microscopy confirmed earlier findings that at rapid growth rates, the G1 phase was short and cell separation occurred at the end of S phase. For some nitrogen sources, the growth rate was greatly decreased, the G1 phase occupied 30-50% of the cell cycle, and cell separation occurred in early G1. In contrast, other nitrogen sources supported low growth rates without any significant increase in G1 duration. The method described allows manipulation of the length of G1 and the relative cell cycle position of S phase in wild-type cells. Cell mass was measured by flow cytometry as scattered light and as protein-associated fluorescence. The extensions of G1 were not related to cell mass at entry into S phase. Our data do not support the hypothesis that the cells must reach a certain fixed, critical mass before entry into S. We suggest that cell mass at the G1/S transition point is variable and determined by a set of molecular parameters. In the present experiments, these parameters were influenced by the different nitrogen sources in a way that was independent of the actual growth rate.  (+info)

Plasmid replication initiator protein RepD increases the processivity of PcrA DNA helicase. (6/17470)

The replication initiator protein RepD encoded by the Staphylococcus chloramphenicol resistance plasmid pC221 stimulates the helicase activity of the Bacillus stearothermophilus PcrA DNA helicase in vitro. This stimulatory effect seems to be specific for PcrA and differs from the stimulatory effect of the Escherichia coli ribosomal protein L3. Whereas L3 stimulates the PcrA helicase activity by promoting co-operative PcrA binding onto its DNA substrate, RepD stimulates the PcrA helicase activity by increasing the processivity of the enzyme and enables PcrA to displace DNA from a nicked substrate. The implication of these results is that PcrA is the helicase recruited into the replisome by RepD during rolling circle replication of plasmids of the pT181 family.  (+info)

SOS and UVM pathways have lesion-specific additive and competing effects on mutation fixation at replication-blocking DNA lesions. (7/17470)

Escherichia coli cells have multiple mutagenic pathways that are induced in response to environmental and physiological stimuli. Unlike the well-investigated classical SOS response, little is known about newly recognized pathways such as the UVM (UV modulation of mutagenesis) response. In this study, we compared the contributions of the SOS and UVM pathways on mutation fixation at two representative noninstructive DNA lesions: 3,N4-ethenocytosine (epsilonC) and abasic (AP) sites. Because both SOS and UVM responses are induced by DNA damage, and defined UVM-defective E. coli strains are not yet available, we first constructed strains in which expression of the SOS mutagenesis proteins UmuD' and UmuC (and also RecA in some cases) is uncoupled from DNA damage by being placed under the control of a heterologous lac-derived promoter. M13 single-stranded viral DNA bearing site-specific lesions was transfected into cells induced for the SOS or UVM pathway. Survival effects were determined from transfection efficiency, and mutation fixation at the lesion was analyzed by a quantitative multiplex sequence analysis procedure. Our results suggest that induction of the SOS pathway can independently elevate mutagenesis at both lesions, whereas the UVM pathway significantly elevates mutagenesis at epsilonC in an SOS-independent fashion and at AP sites in an SOS-dependent fashion. Although mutagenesis at epsilonC appears to be elevated by the induction of either the SOS or the UVM pathway, the mutational specificity profiles for epsilonC under SOS and UVM pathways are distinct. Interestingly, when both pathways are active, the UVM effect appears to predominate over the SOS effect on mutagenesis at epsilonC, but the total mutation frequency is significantly increased over that observed when each pathway is individually induced. These observations suggest that the UVM response affects mutagenesis not only at class 2 noninstructive lesions (epsilonC) but also at classical SOS-dependent (class 1) lesions such as AP sites. Our results add new layers of complexity to inducible mutagenic phenomena: DNA damage activates multiple pathways that have lesion-specific additive as well as suppressive effects on mutation fixation, and some of these pathways are not directly regulated by the SOS genetic network.  (+info)

Chromatin structure: a property of the higher structures of chromatin and in the time course of its formation during chromatin replication. (8/17470)

The action of a number of enzymes and metals on one nuclear preparation were interpreted in terms of the existence of a fragile but highly DNAase-I resistant feature of chromatin superstructure. The generation of this DNAase-I resistance feature of chromatin was then followed during normal DNA synthesis in the regenerating rat liver by following the disappearance of a transitory DNAase-I susceptible state. This transitory, DNAase-I susceptible state appears to be extremely similar to the post-synthetic, DNAase-I susceptible state that has been described in He La32.  (+info)

p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase delta at the G1/S phase transition.
Project Title: Development of high throughput assay for screening of novel DNA replication inhibitors for therapeutic purposes Supervisors: Professor Christian Speck, Professor David Rueda Funding: Tuition fees plus £21,000 pa stipend for 3.5 years Date posted: 09 July 2021 Closing date: 04 August 2021 The student will develop a fluorescence-based assay to identify novel DNA replication inhibitors for anti-cancer therapy. Inhibitors will be consequently characterised for their impact on the multi-step DNA replication process and on cancer cell growth. This interdisciplinary project will train the student in biochemistry, biophysics and drug screening. Project details , LMS 3.5-year Studentships , Apply ...
A number of proteins have been isolated from human cells on the basis of their ability to support DNA replication in vitro of the simian virus 40 (SV40) origin of DNA replication. One such protein, replication factor C (RFC), functions with the proliferating cell nuclear antigen (PCNA), replication protein A (RPA), and DNA polymerase delta to synthesize the leading strand at a replication fork. To determine whether these proteins perform similar roles during replication of DNA from origins in cellular chromosomes, we have begun to characterize functionally homologous proteins from the yeast Saccharomyces cerevisiae. RFC from S. cerevisiae was purified by its ability to stimulate yeast DNA polymerase delta on a primed single-stranded DNA template in the presence of yeast PCNA and RPA. Like its human-cell counterpart, RFC from S. cerevisiae (scRFC) has an associated DNA-activated ATPase activity as well as a primer-template, structure-specific DNA binding activity. By analogy with the phage T4 and ...
TY - JOUR. T1 - The DNA Replication Program Is Altered at the FMR1 Locus in Fragile X Embryonic Stem Cells. AU - Gerhardt, Jeannine. AU - Tomishima, Mark J.. AU - Zaninovic, Nikica. AU - Colak, Dilek. AU - Yan, Zi. AU - Zhan, Qiansheng. AU - Rosenwaks, Zev. AU - Jaffrey, Samie R.. AU - Schildkraut, Carl L.. PY - 2014/1/9. Y1 - 2014/1/9. N2 - Fragile X syndrome (FXS) is caused by a CGG repeat expansion in the FMR1 gene that appears to occur during oogenesis and during early embryogenesis. One model proposes that repeat instability depends on the replication fork direction through the repeats such that (CNG)n hairpin-like structures form, causing DNA polymerase to stall and slip. Examining DNA replication fork progression on single DNA molecules at the endogenous FMR1 locus revealed that replication forks stall at CGG repeats in human cells. Furthermore, replication profiles of FXS human embryonic stem cells (hESCs) compared to nonaffected hESCs showed that fork direction through the repeats is ...
Replication of the two template strands at eukaryotic cell DNA replication forks is a highly coordinated process that ensures accurate and efficient genome duplication. Biochemical studies, principally of plasmid DNAs containing the Simian Virus 40 origin of DNA replication, and yeast genetic studies have uncovered the fundamental mechanisms of replication fork progression. At least two different DNA polymerases, a single-stranded DNA-binding protein, a clamp-loading complex, and a polymerase clamp combine to replicate DNA. Okazaki fragment synthesis involves a DNA polymerase-switching mechanism, and maturation occurs by the recruitment of specific nucleases, a helicase, and a ligase. The process of DNA replication is also coupled to cell-cycle progression and to DNA repair to maintain genome integrity.. ...
Previous genetic studies in yeast suggested that Pol ε plays an important role during chromosomal DNA replication [1, 7-9]. However, because the amino-terminal portion of Pol ε, that is required for its DNA polymerase- and exonuclease activities, is dispensable for yeast DNA replication, repair, and viability [15, 16, 27], the role of Pol ε during DNA replication has remained obscure. This study explores this role using an in vitro Xenopus DNA replication system and wild type and mutant forms of r-xPol ε holoenzyme. Here we show that the DNA replication defect in xPol ε-depleted Xenopus egg extracts is readily corrected by native (n-xPol ε) (data not shown and [22]) or recombinant xPol ε (r-xPol ε) holoenzyme or the p260-p60 Pol ε sub-complex, but not by p260ΔCat holoenzyme, p260 DN, p260 or p260-p12-p17 (Fig. 4). Because the former enzymes are polymerase proficient, while p260ΔCat holoenzyme and p260 DN are polymerase-deficient, although these preparations contained a small amount of ...
Mutations in DNA replication initiator genes in both prokaryotes and eukaryotes lead to a pleiotropic array of phenotypes, including defects in chromosome segregation, cytokinesis, cell cycle regulation and gene expression. For years, it was not clear whether these diverse effects were indirect consequences of perturbed DNA replication, or whether they indicated that DNA replication initiator proteins had roles beyond their activity in initiating DNA synthesis. Recent work from a range of organisms has demonstrated that DNA replication initiator proteins play direct roles in many cellular processes, often functioning to coordinate the initiation of DNA replication with essential cell-cycle activities. The aim of this review is to highlight these new findings, focusing on the pathways and mechanisms utilized by DNA replication initiator proteins to carry out a diverse array of cellular functions.
A complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (DnaB or MCM complex) precedes the DNA synthetic machinery and unwinds the duplex parental DNA in cooperation with the SSB or RPA. On the leading strand, replication occurs continuously in a 5 to 3 direction, whereas on the lagging strand, DNA replication occurs discontinuously by synthesis and joining of short Okazaki fragments. In prokaryotes, the leading strand replication apparatus consists of a DNA polymerase (pol III core), a sliding clamp (beta), and a clamp loader (gamma delta complex). The DNA primase (DnaG) is needed to form RNA primers. Normally, during replication of the lagging-strand DNA template, an RNA primer is removed either by an RNase H or by the 5 to 3 exonuclease activity of DNA pol I, and the DNA ligase joins the Okazaki fragments. In eukaryotes, three DNA polymerases (alpha, ...
A complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (DnaB or MCM complex) precedes the DNA synthetic machinery and unwinds the duplex parental DNA in cooperation with the SSB or RPA. On the leading strand, replication occurs continuously in a 5 to 3 direction, whereas on the lagging strand, DNA replication occurs discontinuously by synthesis and joining of short Okazaki fragments. In prokaryotes, the leading strand replication apparatus consists of a DNA polymerase (pol III core), a sliding clamp (beta), and a clamp loader (gamma delta complex). The DNA primase (DnaG) is needed to form RNA primers. Normally, during replication of the lagging-strand DNA template, an RNA primer is removed either by an RNase H or by the 5 to 3 exonuclease activity of DNA pol I, and the DNA ligase joins the Okazaki fragments. In eukaryotes, three DNA polymerases (alpha, ...
TY - JOUR. T1 - In vitro complementation as an assay for purification of adenovirus DNA replication proteins. AU - Ostrove, J. M.. AU - Rosenfeld, P.. AU - Williams, J.. AU - Kelly, T.. PY - 1983. Y1 - 1983. N2 - As an approach to the purification of adenovirusencoded DNA replication proteins, we have developed in vitro complementation assays that make use of viral mutants defective in DNA replication in vivo. Nuclear extracts prepared from cells infected with H5ts36 or H5ts125, two such mutants belonging to different complementation groups, were found to be defective in viral DNA replication in vitro. However, replication activity could be restored by mixing the two extracts. Replication activity in either extract also could be restored by addition of appropriate replication-deficient fractions purified from cells infected with wild-type adenovirus. By using such assays, H5ts36- and H5ts125-complementing activities were extensively purified. As expected, purified H5ts125-complementing activity ...
DNA replication is a tightly regulated multistep process that requires the sequential action of several protein complexes that select DNA replication origins, recruit on these origins the DNA replication fork helicase that once activated, unwinds and duplicates the DNA. These events must be tightly coupled to cell cycle progression to ensure that DNA replication occurs once and only once per cell cycle.. DNA replication is thus temporally separated into two steps that are controlled by Cyclin-Dependent Kinase (CDK) activity. The first step, which occurs in mitosis and during the G1 phase of the cell cycle, when Cdk activity is low, involves the loading of a double hexameric Mcm2-7 (minichromosome maintenance 2-7) complex on the chromatin as part of the prereplicative complex (pre-RC) (Evrin et al. 2009; Remus et al. 2009; Gambus et al. 2011; Deegan and Diffley 2016). Pre-RC formation requires several loading factors including the hexameric Origin Recognition Complex (ORC-1-6), and Cdc6 and Cdt1 ...
Proper coordination of the functions at the DNA replication fork is vital to the normal functioning of a cell. Specifically the precise coordination of helicase and polymerase activity is crucial for efficient passage though S phase. The Ctf4 protein has been shown to be a central member of the replication fork and links the replicative MCM helicase and DNA polymerase [alpha] primase. In addition, it has been implicated as a member of a complex that promotes replication fork stability, the Fork Protection Complex (FPC), and as being important for sister chromatid cohesion. As such, understanding the role of Ctf4 within the context of a multicellular organism will be integral to our understanding of its potential role in developmental and disease processes. We find that Drosophila Ctf4 is a conserved protein that interacts with members of the GINS complex, Mcm2, and Polymerase [alpha] primase. Using in vivo RNAi knockdown of CTF4 in Drosophila we show that Ctf4 is required for viability, S phase ...
Initiation of DNA replication during the mitotic cell cycle requires the activation of a cyclin-dependent protein kinase (CDK). The B-type cyclins Clb5 and Clb6 are the primary activators of the S phase function of the budding yeast CDK Cdc28. However, in mitotically growing cells this role can be fulfilled by the other B-type cyclins Clb1-Clb4. We report here that cells undergoing meiotic development also require Clb dependent CDK activity for DNA replication. Diploid clb5/clb5 clb6/clb6 mutants are unable to perform premeiotic DNA replication. Despite this defect, the mutant cells progress into the meiotic program and undergo lethal segregation of unreplicated DNA suggesting that they fail to activate a checkpoint that restrains meiotic M phase until DNA replication is complete. We have found that a DNA replication checkpoint dependent on the ATM homolog MEC1 operates in wild-type cells during meiosis and can be invoked in response to inhibition of DNA synthesis. Although cells that lack clb5 and clb6
Dna replication diagram ncert. This process involves multiple steps that have to proceed in a specific sequence to generate the desired product. Dna replication takes place in order to prepare cell for division. Dna replication is an important process that occurs during cell division. Watson and crick dna model. The dna replication in eukaryotes is similar to the dna replication in prokaryotes. Dna replication enzymes have the ability to quicken reactions and build up or break down the items that they act upon. ,br, this creates some additional complications at the replicating fork. There can be dna replication without cell division. Last updated on january 3, 2020 by sagar aryal. Ncert book for class 12 biology chapter 6 molecular basis of inheritance is available for reading or download on this page. (a) dna is a macromolecule since two strands of dna cannot be separated in its entire length (due to very high energy requirement), the replication occur in small replication fork. [image will be ...
Schmid, Jonas. Histone ubiquitination by the DNA damage response is required for efficient DNA replication in unperturbed S-phase. 2018, University of Zurich, Faculty of Science. ...
please provide good explanation1- compare the dna replication process in cells with the process occurring in the pcr, Hire Biology Expert, Ask Academics Expert, Assignment Help, Homework Help, Textbooks Solutions
Supplementary MaterialsPeer Review File 41467_2017_632_MOESM1_ESM. Abstract mRNA-processing (P-) body are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete match of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment. The key P-body protein Lsm1 controls the large quantity of and mRNAs to prevent their toxic accumulation during replication stress. Accumulation of mRNA causes aberrant downregulation of a network of genes critical for DNA replication stress resistance and prospects to harmful acetaldehyde accumulation. Our data reveal the scope and the targets of regulation by P-body proteins during the DNA replication stress response. ...
To examine the basis for the evolutionary selection for codirectionality of replication and transcription in Escherichia coli, electron microscopy was used to visualize replication from an inducible ColE1 replication origin inserted into the Escherichia coli chromosome upstream (5) or downstream (3) of rrnB, a ribosomal RNA operon. Active rrnB operons were replicated either in the same direction in which they were transcribed or in the opposite direction. In either direction, RNA polymerases were dislodged during replication. When replication and transcription were codirectional, the rate of replication fork movement was similar to that observed in nontranscribed regions. When replication and transcription occurred in opposite directions, replication fork movement was reduced. ...
Chapter 3: DNA Replication Models of DNA replication: Meselson-Stahl Experiment DNA synthesis and elongation DNA polymerases Origin and initiation of DNA replication Prokaryote/eukaryote models (circular/linear chromosomes) Telomere replication Slideshow 29909 by JasminFlorian
Polo-like kinase 1 (Plk1) plays pivotal roles in mitosis; however, little is known about its function in S phase. In this study, we show that inhibition of Plk1 impairs DNA replication and results in slow S-phase progression in cultured cancer cells. We have identified origin recognition complex 2 (Orc2), a member of the DNA replication machinery, as a Plk1 substrate and have shown that Plk1 phosphorylates Orc2 at Ser188 in vitro and in vivo. Furthermore, Orc2-S188 phosphorylation is enhanced when DNA replication is under challenge induced by ultraviolet, hydroxyurea, gemcitabine, or aphidicolin treatment. Cells expressing the unphosphorylatable mutant (S188A) of Orc2 had defects in DNA synthesis under stress, suggesting that this phosphorylation event is critical to maintain DNA replication under stress. To dissect the mechanism pertinent to this observation, we showed that Orc2-S188 phosphorylation associates with DNA replication origin and that cells expressing Orc2-S188A mutant fail to ...
TY - JOUR. T1 - Genetic control of the cell division cycle in yeast. II. Genes controlling DNA replication and its initiation. AU - Hartwell, Leland H.. PY - 1971/7/14. Y1 - 1971/7/14. N2 - Temperature-sensitive mutations occurring in two unlinked complementation groups, cdc4 and cdc8, are recessive and result in a defect in DNA replication at the restrictive temperature. Results obtained with synchronous cultures suggest that cdc4 functions in the initiation of DNA replication and cdc8 functions in the propagation of DNA replication. From the behavior of mutant strains carrying lesions in cdc4, or in cdc8, or in both genes it is concluded that: (1) nuclear division and cell separation in yeast are dependent upon prior DNA replication; (2) a cellular clock controls bud initiation and the running of this clock is independent of the other events in the cycle, DNA replication, nuclear division and cell separation; (3) premature bud initiation is normally prevented as a consequence of the successful ...
TY - JOUR. T1 - Repetitive lagging strand DNA synthesis by the bacteriophage T4 replisome. AU - Spiering, Michelle M.. AU - Nelson, Scott W.. AU - Benkovic, Stephen J.. PY - 2008. Y1 - 2008. N2 - Our studies on the T4 replisome build on the seminal work from the Alberts laboratory. They discovered essentially all the proteins that constitute the T4 replisome, isolated them, and measured their enzymatic activities. Ultimately, in brilliant experiments they reconstituted in vitro a functioning replisome and in the absence of structural information created a mosaic as to how such a machine might be assembled. Their consideration of the problem of continuous leading strand synthesis opposing discontinuous lagging strand synthesis led to their imaginative proposal of the trombone model, an illustration that graces all textbooks of biochemistry. Our subsequent work deepens their findings through experiments that focus on defining the kinetics, structural elements, and protein-protein contacts ...
Flow cytometry, a method for measuring DNA content, also gives information about the cell cycle. Non-cycling cells are said to be in the G0 stage. For cycling cells, it is usual to define four distinct phases of the cell cycle. Mitosis (M phase) is followed by the G1 phase (gap 1). During this phase the cell continuously grows but does not replicate its DNA. When the cell starts to make new DNA it has entered the S (DNA synthesis) phase. The completion of DNA synthesis is followed by the G2 phase (gap 2), during which cell growth continues and proteins are synthesised in preparation for mitosis [1]. Flow cytometry has been shown to be very suitable for determining the DNA replication stages in seeds [2,3,10,11,16,17,18]. In commercial practice, sugar beet seeds are often washed/soaked and treated with fungicides before sowing. These treatments are intended to leach out the soluble inhibitors from the pericarp and to control damping off, which, in turn, improve seed performance in the field ...
AMONG the genetic and epigenetic changes to genomes, changes in ploidy are the most drastic, and as such, polyploidy is not tolerated by most animal species (Li et al. 2009a). A recent study of tetraploid yeast suggests that the deleterious effects of ploidy change are due to the uncoordinated scaling of the spindle pole body, spindle, and kinetochore, thus resulting in genetic instability (GIN) (Storchova et al. 2006). However, ploidy changes occur in every sexual cycle of all eukaryotes and are associated with the inclusion or exclusion of an entire set of chromosome homologs that significantly alters the DNA repair capacity. Little is known about whether DNA damage response is regulated differently in haplophase and diplophase during sexual cycles.. DNA replication stress, induced by oncogene activation, genotoxic stress, or defects in the DNA replication machinery, is believed to cause GIN that accelerates tumorigenesis (Halazonetis et al. 2008). However, DNA replication stress does not ...
Dates: 7 - 10 May 2018 Registration: 26 Mar 18 Abstract: 12 Feb 18 Event webpage: Aim:There has been tremendous progress in the past few years regarding our understanding of DNA replication in eukaryotes, both yeast and mammals. Many important questions in the field are poised to be answered within the next decade. These include understanding DNA replication at the biochemical and three-dimensional protein structure levels. In addition, studies using high throughput technologies at the cellular and organismal levels are poised to answer how accurate replication of the genome is ensured by controlling origin firing in space and time.Several human diseases, including cancer, have already been linked to DNA replication stress, a term that refers to perturbations in DNA replication. Thus, a better understanding of how cells respond to DNA replication stress will help us understand disease development and responses to therapy. By bringing ...
Molecular mechanism of DNA replication. Two distinct Polymerases - a and d, appear to function at the eukaryotic growing fork.Polymerase d (pol. Before replication can start, the DNA has to be made available as a template. This process is called semiconservative replication because one of the old strands is conserved in the new DNA double helix. Notes # Replication of Circular DNA Molecules: Circular DNA molecules occur in both prokaryotes and eukaryotes. Next lesson. DNA replication would not occur without enzymes that catalyze various steps in the process. However, the interaction of the initiation proteins with the ds-DNA is more complex. RNA polymerase requires a number of helper proteins to bind to DNA and initiate RNA Eukaryotic DNA replication, also reviewed in more detail in Chapter 3, Features of Host Cells: Cellular and Molecular Biology Review, is also carried out by DNA polymerases and other proteins within the nucleus. In eukaryotes, the situation is different in a number of ...
Mammalian mitochondria operate multiple mechanisms of DNA replication. In many cells and tissues a strand-asynchronous mechanism predominates over coupled leading and lagging-strand DNA synthesis. However, little is known of the factors that control or influence the different mechanisms of replication, and the idea that strand-asynchronous replication entails transient incorporation of transcripts (aka bootlaces) is controversial. A firm prediction of the bootlace model is that it depends on mitochondrial transcripts. Here, we show that elevated expression of Twinkle DNA helicase in human mitochondria induces bidirectional, coupled leading and lagging-strand DNA synthesis, at the expense of strand-asynchronous replication; and this switch is accompanied by decreases in the steady-state level of some mitochondrial transcripts. However, in the so-called minor arc of mitochondrial DNA where transcript levels remain high, the strand-asynchronous replication mechanism is instated. Hence, replication ...
Chromosome replication in eukaryotic cells is regulated in a highly complex fashion in order to maintain the integrity of the genome from one generation to the next. DNA replication forks are established at different moments in time during S‐phase from multiple origins on each chromosome, yet initiation at each origin can occur just once, so that a single copy of the genome is generated in each round of a typical cell cycle (Blow and Dutta, 2005). This is achieved by dividing the cell cycle into a period when prereplication complexes (pre‐RCs) of proteins essential for initiation are assembled at origins but cannot be activated, and a subsequent and mutually exclusive period when pre‐RCs can be activated but can no longer form (Diffley et al, 1994). At each origin, the pre‐RC is lost during initiation, so that each region of the chromosome is replicated precisely once during each cell cycle.. The key event in the formation of pre‐RCs-also known as the licensing of origins-is the ...
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for natural inheritance. The process starts when one double-stranded DNA molecule produces two identical copies of the molecule. The cell cycle (mitosis) also pertains to the DNA replication/reproduction process. DNA replication, in eukaryotes, is controlled within the context of the cell cycle. As the cell grows and divides, it goes through stages in the cell cycle; DNA replication occurs during the S phase (synthesis phase). Whereas bacteria do not go through an exact cell cycle but instead, they continuously copy their DNA. The research conducted in this study was to see if, in fact, that cell size had anything to do with the initiation of DNA replication in bacteria. The objectives and hypothesis was clearly stated in the paper. In order to find the answer to their question, the researchers used Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in their experiment. ...
Plays a key role in the initiation and regulation of chromosomal replication. Binds in an ATP-dependent fashion to the origin of replication (oriC) to initiate formation of the DNA replication initiation complex exactly once per cell cycle. Binds the DnaA box (consensus sequence 5-TTATC[CA]A[CA]A-3); subsequent binding of DNA polymerase III subunits leads to replisome formation. The DnaA-ATP form converts to DnaA-ADP; once converted to ADP the protein cannot initiate replication, ensuring only 1 round of replication per cell cycle. DnaA can inhibit its own gene expression as well as that of other genes such as dam, rpoH, ftsA and mioC.
Cyclin-dependent kinases (CDKs) regulate the progression of the cell cycle in eukaryotes. One of the major roles of CDK is to promote chromosomal DNA replication. However, how CDKs promote DNA replication has been a long-standing question, because all the essential CDK substrates in DNA replication have not been identified yet. Recently Sld2 and Sld3 were identified as essential substrates of CDKs in the initiation step of DNA replication in budding yeast. Moreover, bypass of their phosphorylations is sufficient to promote DNA replication. Phosphorylation of Sld2 and Sld3 by CDKs enhances the formation of complex(es) with a BRCT (BRCA1 C-Terminal)-containing replication protein, Dpb11. We further propose that multiple phosphorylation by CDKs controls this process in budding yeast. Even though Sld3 orthologues in multicellular eukaryotes have not been identified, similar complex formation and, therefore, a similar mechanism of initiation control might be employed in eukaryotes.
The T4 bacteriophage dda protein is a DNA-dependent ATPase and DNA helicase that is the product of an apparently nonessential T4 gene. We have examined its effects on in vitro DNA synthesis catalyzed by a purified, multienzyme T4 DNA replication system. When DNA synthesis is catalyzed by the T4 DNA polymerase on a single-stranded DNA template, the addition of the dda protein is without effect whether or not other replication proteins are present. In contrast, on a double-stranded DNA template, where a mixture of the DNA polymerase, its accessory proteins, and the gene 32 protein is required, the dda protein greatly stimulates DNA synthesis. The dda protein exerts this effect by speeding up the rate of replication fork movement; in this respect, it acts identically with the other DNA helicase in the T4 replication system, the T4 gene 41 protein. However, whereas a 41 protein molecule remains bound to the same replication fork for a prolonged period, the dda protein seems to be continual
Maintaining replication fork integrity is vital to preserve genomic stability and avoid cancer. Physical DNA damage and altered nucleotide or protein pools represent replication obstacles, generating replicative stress. Numerous cellular responses have evolved to ensure faithful DNA replication despite such challenges. Understanding those responses is essential to understand and prevent or treat replication-associated diseases, such as cancer.. Re-priming is a mechanism to allow resumption of DNA synthesis past a fork-stalling lesion. This was recently suggested in yeast and explains the formation of gaps during DNA replication on damaged DNA. Using a combination of assays, we indicate the existence of re-priming also in human cells following UV irradiation.. The gap left behind a re-primed fork must be stabilised to avoid replication-associated collapse. Our results show that the checkpoint signalling protein CHK1 is dispensable for stabilisation of replication forks after UV irradiation, ...
The DNA replication checkpoint is a complex signal transduction pathway, present in all eukaryotic cells, that functions to maintain genomic integrity and cell viability when DNA replication is perturbed. In Schizosaccharomyces pombe the major effector of the replication checkpoint is the protein kinase Cds1. Activation of Cds1 is known to require the upstream kinase Rad3 and the mediator Mrc1, but the biochemical mechanism of activation is not well understood. We report that the replication checkpoint is activated in two stages. In the first stage, Mrc1 recruits Cds1 to stalled replication forks by interactions between the FHA domain of Cds1 and specific phosphorylated Rad3 consensus sites in Mrc1. Cds1 is then primed for activation by Rad3-dependent phosphorylation. In the second stage, primed Cds1 molecules dimerize via phospho-specific interactions mediated by the FHA domains and are activated by autophosphorylation. This two-stage activation mechanism for the replication checkpoint allows for rapid
The cohesin complex holds together newly-replicated chromatids and is involved in diverse pathways that preserve genome integrity. We show that in budding yeast, cohesin is transiently recruited to active replication origins and it spreads along DNA as forks progress. When DNA synthesis is impeded, cohesin accumulates at replication sites and is critical for the recovery of stalled forks. Cohesin enrichment at replication forks does not depend on H2A(X) formation, which differs from its loading requirements at DNA double-strand breaks (DSBs). However, cohesin localization is largely reduced in rad50delta mutants and cells lacking both Mec1 and Tel1 checkpoint kinases. Interestingly, cohesin loading at replication sites depends on the structural features of Rad50 that are important for bridging sister chromatids, including the CXXC hook domain and the length of the coiled-coil extensions. Together, these data reveal a novel function for cohesin in the maintenance of genome integrity during S phase. Scc1
DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during ...
DNA-skadande ämnen är vanligt i cancerbehandling, då snabbt växande celler, såsom cancerceller är betydligt känsligare än normala celler för DNA skador. En grupp av ämnen som vanligen används i cancerbehandling är korsbindare av DNA. Dessa ämnen kommer reagera två gånger med DNA och skapa två bindningar mitt emot varandra. DNA strängen, som består av två delar, måste kunna separeras och kopieras (replikation) på ett tillförlitligt sätt för att cellerna ska kunna dela sig och bli flera. DNA strängen måste också kunna dela sig och bli avläst rätt för att nya proteiner ska kunna bildas (transkription). När korsbindarna har bundit till DNA strängarna, hindrar detta deras separation och därigenom förhindras även avläsningen och kopieringen. För att göra undersökningarna av DNA korsbindande ämnen ännu lite svårare, så ger korsbindare flera olika typer av skador. Dels kan det bli flera olika typer av korsbindningar, både mellan två DNA-strängar (ICL) vilket ...
Professor Emeritus Department of Biochemistry Rosalind and Morris Goodman Cancer Centre [email protected] 1979 - PhD, McGill University Research Interests Isolation and characterization of mammalian origins of DNA replication Our primary research interest is in the molecular basis of the mechanisms regulating mammalian DNA replication. Eukaryotic chromosomes are organized into multiple replication units that initiate replication only one per cell cycle. The mechanism that prevents the reinitiation of replication of DNA that has been previously replicated is unknown. Among the major questions about mammalian DNA replication are: 1) whether initiation occurs at specific DNA sequences (replication origins), and 2) what are the molecular features of these sequences. Using the instability of replication loops as a method for the isolation of active replication origins, we have purified and cloned DNA sequences that contain origins of replication. In this manner we have generated libraries of monkey and
Professor Emeritus Department of Biochemistry Rosalind and Morris Goodman Cancer Centre [email protected] 1979 - PhD, McGill University Research Interests Isolation and characterization of mammalian origins of DNA replication Our primary research interest is in the molecular basis of the mechanisms regulating mammalian DNA replication. Eukaryotic chromosomes are organized into multiple replication units that initiate replication only one per cell cycle. The mechanism that prevents the reinitiation of replication of DNA that has been previously replicated is unknown. Among the major questions about mammalian DNA replication are: 1) whether initiation occurs at specific DNA sequences (replication origins), and 2) what are the molecular features of these sequences. Using the instability of replication loops as a method for the isolation of active replication origins, we have purified and cloned DNA sequences that contain origins of replication. In this manner we have generated libraries of monkey and
We showed previously that DNA replication initiates at multiple sites in the 5-kb histone gene repeating unit in early embryos of Drosophila melanogaster. The present report shows evidence that replication in the same chromosomal region initiates at multiple sites in tissue culture cells as well. First, we analyzed replication intermediates by the two-dimensional gel electrophoretic replicon mapping method and detected bubble-form replication intermediates for all fragments restricted at different sites in the repeating unit. Second, we analyzed bromodeoxyuridine-labeled nascent strands amplified by the polymerase chain reaction method and detected little differences in the size distribution of nascent strands specific to six short segments located at different sites in the repeating unit. These results strongly suggest that DNA replication initiates at multiple sites located within the repeating unit. We also found several replication pause sites located at 5 upstream regions of some histone ...
Human genetic variation is distributed nonrandomly across the genome, though the principles governing its distribution are only partially known. DNA replication creates opportunities for mutation, and the timing of DNA replication correlates with the density of SNPs across the human genome. To enable deeper investigation of how DNA replication timing relates to human mutation and variation, we generated a high-resolution map of the human genomes replication timing program and analyzed its relationship to point mutations, copy number variations, and the meiotic recombination hotspots utilized by males and females. DNA replication timing associated with point mutations far more strongly than predicted from earlier analyses and showed a stronger relationship to transversion than transition mutations. Structural mutations arising from recombination-based mechanisms and recombination hotspots used more extensively by females were enriched in early-replicating parts of the genome, though these ...
TY - JOUR. T1 - H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication. AU - Wu, Rentian. AU - Wang, Zhiquan. AU - Zhang, Honglian. AU - Gan, Haiyun. AU - Zhang, Zhiguo. N1 - Publisher Copyright: © 2016 The Author(s).. PY - 2017/1/9. Y1 - 2017/1/9. N2 - DNA replication is tightly regulated to occur once and only once per cell cycle. How chromatin, the physiological substrate of DNA replication machinery, regulates DNA replication remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d regulates DNA replication in eukaryotic cells. Depletion of Kdm4d results in defects in DNA replication, which can be rescued by the expression of H3K9M, a histone H3 mutant transgene that reverses the effect of Kdm4d on H3K9 methylation. Kdm4d interacts with replication proteins, and its recruitment to DNA replication origins depends on the two prereplicative complex components (origin recognition complex [ORC] and minichromosome ...
A cell-free system has been developed from cells of an Escherichia coli strain, carrying cloned genes 1 (DNA polymerase) and 8 (terminal protein) of bacteriophage PRD1, that catalyzes protein-primed DNA synthesis. DNA synthesis in vitro is entirely dependent upon the addition of PRD1 DNA-terminal protein complex as template, Mg²⁺, and four deoxyribonucleoside triphosphates. The origin and direction of PRD1 DNA replication in vitro were determined by restriction enzyme analysis of ³²P-labeled PRD1 DNA synthesized in this system. Replication starts at either end of the linear PRD1 DNA template. Analysis by alkaline sucrose gradient centrifugation and alkaline agarose gel electrophoresis of DNA synthesized in vitro showed that full-length PRD1 DNA is synthesized. DNA elongation in this system is inhibited by the drug aphidicolin. On the other hand, DNA initiation is inhibited by phenylglyoxal, an arginine-specific α-dicarbonyl reagent. In vitro studies have also demonstrated that linear ...
DNA is the substrate of many cellular processes including DNA replication, transcription and chromatin remodeling. These processes are coordinated to maintain genome integrity and ensure accurate duplication of genetic and epigenetic information. Genome-wide studies have provided evidence of the relationship between transcription and DNA replication timing. A global analysis of DNA replication initiation in T. brucei showed that TbORC1 (subunit of the origin recognition complex, ORC) binding sites are located at the boundaries of transcription units. Although recent studies in T. brucei indicate functional links among DNA replication and transcription, the underlying mechanisms remain unknown. In this study, we adapted an unbiased technology for the identification of replication fork proteins called iPOND (isolation of proteins on nascent DNA) to T. brucei, its first application to a parasite system.The iPOND approach relies on labeling newly replicated DNA with the thymidine analog EdU (5-ethynyl-2′
Worksheets. Dna Replication Worksheet Answers. Dna replication worksheet. 008205436 1 3872ffea623fe664f93effe7b5246723 png. Dna replication coloring worksheet on answer. Dna replication worksheet answer key images source abuse report. Quiz worksheet dna replication study com print review of enzymes bubbles leading and lagging strands worksheet. Dna structure replication animation 7 synthesis quiz genetics animation. 12 3 dna replication. Dna replication fork drawing. Replicate2ans png here are the colors and answers. Unit 4 dna structure replication protein synthesis download file. Biggone Worksheets & Printables
DNA damage can stall the DNA replication machinery, leading to genomic instability. Thus, numerous mechanisms exist to complete genome duplication in the absence of a pristine DNA template, but identification of the enzymes involved remains incomplete. Here, we establish that Primase-Polymerase (PrimPol; CCDC111), an archaeal-eukaryotic primase (AEP) in eukaryotic cells, is involved in chromosomal DNA replication. PrimPol is required for replication fork progression on ultraviolet (UV) lightdamaged DNA templates, possibly mediated by its ability to catalyze translesion synthesis (TLS) of these lesions. This PrimPol UV lesion bypass pathway is not epistatic with the Pol h-dependent pathway and, as a consequence, protects xeroderma pigmentosum variant (XP-V) patient cells from UV-induced cytotoxicity. In addition, we establish that PrimPol is also required for efficient replication fork progression during an unperturbed S phase. These and other findings indicate that PrimPol is an important player ...
The genes encoding two of the subunits of the Saccharomyces cerevisiae origin recognition complex (ORC) have been isolated. Characterization of a temperature-sensitive mutation in the gene encoding the 72-kD subunit of ORC (ORC2) indicates that this protein complex functions early in the DNA replication process. Moreover, ORC derived from orc2ts cells is defective for DNA binding. Others have shown a defect in orc2ts cells in transcriptional silencing at the silent mating-type loci. Consistent with this finding, ORC specifically binds to each of the four mating-type silencers identified in yeast. These findings support the hypothesis that ORC acts as an initiator protein at yeast origins of DNA replication and suggest that ORC also functions in the determination of transcriptional domains. ...
In response to replication stress, a phospho-signaling cascade is activated and required for coordination of DNA repair and replication of damaged templates (intra-S phase checkpoint). How phospho-signaling coordinates the DNA replication stress response is largely unknown. We employed state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) approaches to generate high-coverage and quantitative proteomic and phospho-proteomic profiles during replication stress in yeast, induced by continuous exposure to the DNA alkylating agent methyl methanesulfonate (MMS). We identified 32,057 unique peptides representing the products of 4,296 genes, and 22,061 unique phosphopeptides representing the products of 3,183 genes. 542 phosphopeptides (mapping to 339 genes) demonstrated an abundance change of ≥ 2-fold in response to MMS. The screen enabled detection of nearly all of the proteins known to be involved in the DNA damage response, as well as many novel MMS-induced phosphorylations. We ...
If you are interested in looking at the DNA structure and replication review worksheet, you can do so through many different websites. Acces PDF Dna Replication Worksheet Answers Dna Replication Worksheet Answers This is likewise one of the factors by obtaining the soft documents of this dna replication worksheet answers by online. ____ 1. 4. The new cells then receive the instructions and information needed to function. 3. -What is happening to the DNA molecule in the figure? nucleus before a cell divides. Answer the following questions about DNA replication in complete sentences. 4 0 obj Figure 3. DNA Replication Name _____ Step 1 : After you have completed your DNA keychain, label the bases on the paper model with A, T, G, or C and color the squares to match the bases exactly as they are on your keychain from the bottom to the top. 1. DNA Replication and Transcription Worksheet . Why does DNA need to replicate? Replication occurs in a Theyre the same size and shape, and have the same pattern ...
One of the factors limiting indefinite proliferation of somatic cells is telomere length [1], [2]. Indeed, the inability to fully replicate both strands of a linear DNA molecule is expected to lead to gradual shortening of telomeres in cells that do not express telomerase. Telomere shortening may be even more severe, if the replication machinery fails to reach the telomeric end. Indeed, the highly repetitive primary structure of telomeres [3], the presence of G‐quadruplexes [4], DNA-RNA hybrids [5], [6], and T‐loops [7], as well as the extensive telomeric heterochromatinization [8], challenge the process of terminal DNA replication and make telomeres prone to fork collapse, similar to common fragile sites [9], [10]. Fork collapse within a telomere is unlikely to be resolved by incoming forks or dormant forks, since human telomeres are thought to be devoid of replication origins. Instead, telomere replication is normally dependent on a single origin, located at the subtelomeric regions [11]. ...
One of the factors limiting indefinite proliferation of somatic cells is telomere length [1], [2]. Indeed, the inability to fully replicate both strands of a linear DNA molecule is expected to lead to gradual shortening of telomeres in cells that do not express telomerase. Telomere shortening may be even more severe, if the replication machinery fails to reach the telomeric end. Indeed, the highly repetitive primary structure of telomeres [3], the presence of G‐quadruplexes [4], DNA-RNA hybrids [5], [6], and T‐loops [7], as well as the extensive telomeric heterochromatinization [8], challenge the process of terminal DNA replication and make telomeres prone to fork collapse, similar to common fragile sites [9], [10]. Fork collapse within a telomere is unlikely to be resolved by incoming forks or dormant forks, since human telomeres are thought to be devoid of replication origins. Instead, telomere replication is normally dependent on a single origin, located at the subtelomeric regions [11]. ...
Each cell division, the nuclear DNA must be replicated efficiently and with high accuracy to avoid mutations which can have an effect on cell function. There are three replicative DNA polymerases essential for the synthesis of DNA during replication in eukaryotic cells. DNA polymerase α (Pol α) synthesize short primers required for DNA polymerase δ (Pol δ) and DNA polymerase ε (Pol ε) to carry out the bulk synthesis. The role of Pol δ and Pol ε at the replication fork has been unclear. The aim of this thesis was to examine what role Pol ε has at the replication fork, compare the biochemical properties of Pol δ and Pol ε, and to study the function of the second largest and essential subunit of Pol ε, Dpb2.. To identify where Pol ε replicates DNA in vivo, a strategy was taken where the active site of Pol ε was altered to create a mutator polymerase leaving a unique error-signature. A series of mutant pol ε proteins were purified and analyzed for enzyme activity and fidelity of DNA ...
Biological Function. Although synthesis of the lagging strand involves only half the DNA in the nucleus, the complexity associated with processing Okazaki fragments is about twice that required to synthesize the leading strand. Even in small species such as yeast, Okazaki fragment maturation happens approximately a million times during a single round of DNA replication. Processing of Okazaki fragments is therefore very common and crucial for DNA replication and cell proliferation.. During this process, RNA and DNA primers are removed, allowing the Okazaki fragments to attach to the lagging DNA strand. While this process seems quite simple and repetitive, defects in Okazaki fragment maturation can cause DNA strand breakage which can cause varying forms of chromosome aberrations. Severe defects of Okazaki fragment maturation may halt DNA replication and induce cell death. However, while subtle defects do not affect growth, they do result in future varying forms of genome instabilities. Based on ...
Cdc7-Dbf4 is an essential protein kinase complex required for every single origin firing. As a target of the intra-S checkpoint, Cdc7 kinase activity has also been implicated in the response to replication fork stress, with a role in translesion DNA synthesis (TLS). We have examined the role of Cdc7 in the regulation of replication forks, particularly in response to MMS, which normally stalls replication forks and inhibits late origin firing. We find that replication forks proceed as fast as with no damage along an MMS-damaged template both in cdc7as3 and cdc7-1/mcm5-bob1 cells. However the DNA synthesis in cdc7-1/mcm5-bob1 in MMS is defective, indicated by the slower recovery after MMS by PFGE, suggesting the replication is incomplete. These deregulated forks did not rely on TLS pathway but are dependent on both helicase and E3 ligase function of Rad5 for continued fork progression along MMS-damaged DNA, demonstrating a role for Rad5 at the replication fork. Phosphorylation of MCM2 by DDK was ...
The DNA replication (or origin) licensing machinery ensures precise duplication of the genome and contributes to the regulation of proliferative capacity in metazoa. Using an in vitro fibroblast model system coupled to a cell-free DNA replication assay, we have studied regulation of the origin licensing pathway during exit from and re-entry into the mitotic cell cycle. We show that in the quiescent state (G0) loss of proliferative capacity is achieved in part through down-regulation of the replication licensing factors Cdc6 and Mcm2-7. The origin licensing repressor geminin is absent in quiescent fibroblasts, suggesting that this powerful inhibitor of the licensing machinery is not required to suppress proliferative capacity in G0. Geminin expression is induced at a late stage in the G0-S transition post pre-RC assembly. Ectopic geminin can block re-acquisition of DNA replication competence during re-entry into the cell cycle, indicating that geminin levels must be tightly down-regulated for ...
Interaction of the Escherichia coli Replication Terminator Protein (Tus) with DNA: A Model Derived from DNA-Binding Studies of Mutant Proteins by Surface Plasmon Resonance † Academic Article ...
Abstract: It is critical that chromosomal DNA is precisely duplicated during S phase of the eukaryotic cell cycle, with no sections of DNA left unreplicated or replicated more than once. There is a considerable plasticity in this process because cells license many potential replication origins, of which only a small percentage are used in any one cell cycle, with the others remaining dormant. This means that the usage of replication origins can change under different circumstances. For example, dormant replication origins can be activated when replication forks are inhibited to allow timely completion of the replication programme. A recent paper published in Nature by Courbet et al. [1] illustrates this plasticity of replication origin usage and shows that it is associated with longer-term changes to the organization of chromatin loops. The changes to chromatin organization can then directly affect the way that replication origins are used in subsequent cell cycles.The precise duplication of ...
This thesis analyzes the interaction of two DNA-binding proteins with the plus strand replication origin of bacteriophage f1. The origin has a bipartite structure consisting of a required core origin region and an adjacent A +T- rich enhancer sequence that potentiates replication approximately 100-fold. The core origin binds the initiator protein, and the enhancer contains three binding sites for the E. coli integration host factor (IHF). Both activator proteins bend the DNA sequence to which they bind, implying that together they wrap the origin DNA into a higher order structure that is active in initiation. The replication initiator protein of bacteriophage f1 (gene II protein) is a multifunctional protein that participates in DNA replication at a number of levels. The gene II protein binds to the core origin in a novel two-step fashion. The first binding step involves interaction of two gene II protein molecules with an inverted repeat (β- γ) at the center of the core origin to form a binding
The Rif1 protein, originally identified as a telomere-binding factor in yeast, has recently been implicated in DNA replication control from yeast to metazoans. Here, we show that budding yeast Rif1 protein inhibits activation of prereplication complexes (pre-RCs). This inhibitory function requires t …
Polymerase α is an essential enzyme mainly mediating Okazaki fragment synthesis during lagging strand replication. A specific point mutation in Schizosaccharomyces pombe polymerase α named swi7-1, abolishes imprinting required for mating-type switching. Here we investigate whether this mutation confers any genome-wide defects. We show that the swi7-1 mutation renders cells hypersensitive to the DNA damaging agents methyl methansulfonate (MMS), hydroxyurea (HU) and UV and incapacitates activation of the intra-S checkpoint in response to DNA damage. In addition we show that, in the swi7-1 background, cells are characterized by an elevated level of repair foci and recombination, indicative of increased genetic instability. Furthermore, we detect novel Swi1-, -Swi3- and Pol α- dependent alkylation damage repair intermediates with mobility on 2D-gel that suggests presence of single-stranded regions. Genetic interaction studies showed that the flap endonuclease Fen1 works in the same pathway as Pol ...
In eukaryotic cells, firing of DNA replication origins normally does not recur until after M phase. This characteristic is thought to be due to the properties of initiation proteins like Orc, Cdc6, and Mcms. Using formaldehyde cross-linking, we show that Cdc6p and Mcm7p associate specifically with replication origins during G1 but not during G2 in S. cerevisiae. Mcm7ps association with origins depends on Cdc6p. Ectopic expression of Cdc6p enables it to associate with origins during G2, but this fails to recruit Mcm7p. Our data suggest that the loading of Mcm proteins onto origins is regulated by two mechanisms: first, by Cdc6p occupancy, and second, by S- and M-CDKs, whose activity during S, G2, and M phases prevents Mcm loading.
The nuclear matrix is considered to play a significant role in the DNA replication of eukaryotic cells, although immediate evidence for such a job is inadequate still. GAL4-RAD and PEBP2B1. Moreover, AML1/ETO inhibited Py DNA replication stimulated by GAL4-RAD and Rabbit Polyclonal to KCNK15 PEBP2B1. The inhibition was particular for replication mediated by GAL4-RAD and PEBP2B1, and proportional to the amount of lack of these activators in the nuclear matrix, recommending a requirement of nuclear matrix concentrating on in the arousal of Py DNA replication by RAD. These email address details are the first ever to recommend a molecular hyperlink between your initiation of DNA replication as well as the nuclear matrix area. Accumulating proof suggests an participation of transcription elements in the legislation of DNA replication in eukaryotic cells. The polyomavirus (Py) DNA replication program is fantastic for elucidating the assignments of transcription elements in DNA replication, as Py DNA ...
In eukaryotes, initiation of DNA replication requires the assembly of a multiprotein prereplicative complex (pre-RC) at the origins. We recently reported that a WD repeat-containing protein, origin recognition complex (ORC)-associated (ORCA/LRWD1), plays a crucial role in stabilizing ORC to chromati …
def: A heterotetrameric DNA polymerase complex that catalyzes processive DNA synthesis in the absence of PCNA, but is further stimulated in the presence of PCNA. The complex contains a large catalytic subunit and three small subunits, and is best characterized in Saccharomyces, in which the subunits are named Pol2p, Dpb2p, Dpb3p, and Dpb4p. Some evidence suggests that DNA polymerase epsilon is the leading strand polymerase; it is also involved in nucleotide-excision repair and mismatch repair. [PMID:15814431, PMID:9745046 ...
the nucleus, the complexity associated with processing Okazaki fragments is about twice that required to synthesize the leading strand ... Even in small species such as yeast, Okazaki fragment maturation happens approximately a million times during a single round of DNA replication ... Processing of Okazaki fragments is therefore very common and crucial for DNA replication and cell proliferation ...
Pif1, an evolutionarily conserved helicase, negatively regulates telomere length by removing telomerase from chromosome ends. Pif1 has also been implicated in DNA replication processes Such as Okazaki fragment maturation and replication fork pausing. We find that overexpression of Saccharomyces cervisiae results in dose-dependent. growth inhibition. Strong overexpression causes relocalization of the DNA damage response factors Rfa1 and Mre11 into nuclear foci and activation of the Rad53 DNA damage checkpoint kinase, indicating that. the toxicity is caused by accumulation of DNA-damage. We screened the complete set of similar to 4800 haploid gene deletion mutants and found that moderate overexpression of PIF1, which is only mildly toxic oil its own, causes growth defects in strains with Mutations in genes involved in DNA replication and the DNA damage response. Interestingly, we find that telomerase-deficient strains are also sensitive to PIF1 overexpression. Cur data are consistent with a model ...
The maintenance of genome integrity is critical for the suppression of cancer and premature ageing. Only recently has it become appreciated that DNA replication stress is a crucial driver of genomic instability. The timely progression of replisomes can be disrupted by lesions and secondary structures in the template, by bound proteins and by conflicts with the transcription machinery. A prolonged pause of the replisome then exposes single stranded DNA, which, due to its recombinogenic nature, can lead to genome rearrangements, fragile site expression and cell death. Importantly, some cancers present excessive endogenous levels of replication stress, which can be exploited for their clearance. In this conference, we aim to bring together scientists studying DNA replication and repair, with those interested in how DNA damage can influence cancer and ageing.. Key Sessions. ...
Liver regeneration studies with transgenic mice demonstrated that FoxM1B regulates the onset of hepatocyte DNA replication and mitosis by stimulating expression of cell cycle genes (10, 22, 23, 26). In this study, we used Alb-Cre recombinase to generate a hepatocyte-specific deletion of the Foxm1b gene and demonstrated that Foxm1b is required for normal levels of hepatocyte DNA replication and is essential for mitosis in regenerating liver. We found no significant increase in hepatocyte apoptosis in regenerating Alb-Cre Foxm1b−/− liver (data not shown), suggesting that Foxm1b is required for hepatocyte proliferation but not survival. Reduced DNA replication in regenerating Foxm1b−/− hepatocytes coincided with sustained increase in nuclear staining of the Cdk inhibitor p21 protein between 24 and 40 h after PHx. This increase in nuclear p21 levels and a reduction in Cdc25A phosphatase expression resulted in decreased activation of Cdk2 kinase (Fig. 6G). Cyclin E/A-Cdk2 complex cooperates ...
Purpose.: Diabetic retinopathy fails to halt after cessation of hyperglycemic insult, and a vicious cycle of mitochondria damage continues. The aim of our study was to investigate the effect of termination of hyperglycemia on retinal mtDNA replication, and elucidate the mechanism responsible for the continued mtDNA damage. Methods.: Polymerase gamma 1 (POLG1), the catalytic subunit of the mitochondrial DNA replication enzyme, and the damage to the displacement loop region of mtDNA (D-loop) were analyzed in the retina from streptozotocin-diabetic rats maintained in poor glycemic control (PC, glycated hemoglobin ∼11%) or in good glycemic control (GC, glycated hemoglobin ∼6%) for 6 months, or in PC for three months followed by GC for three months (Rev). To understand the mechanism DNA methylation status of POLG1 promoter was investigated by methylation-specific PCR. The key parameters were confirmed in the isolated retinal endothelial cells exposed to high glucose, followed by normal glucose. ...
Break-induced replication (BIR) repairs one-ended double-strand breaks in DNA similar to those formed by replication collapse or telomere erosion, and it has been implicated in the initiation of genome instability in cancer and other human diseases1,2. Previous studies have defined the enzymes that are required for BIR1-5; however, understanding of initial and extended BIR synthesis, and of how the migrating D-loop proceeds through known replication roadblocks, has been precluded by technical limitations. Here we use a newly developed assay to show that BIR synthesis initiates soon after strand invasion and proceeds more slowly than S-phase replication. Without primase, leading strand synthesis is initiated efficiently, but is unable to proceed beyond 30 kilobases, suggesting that primase is needed for stabilization of the nascent leading strand. DNA synthesis can initiate in the absence of Pif1 or Pol32, but does not proceed efficiently. Interstitial telomeric DNA disrupts and terminates BIR
The studies described in this thesis are concerned with the replication of the small icosahedral phage DNAs. Three aspects of DNA multiplication are presented.;(1) An important problem in DNA replication is the mechanism by which polynucleotide chains are initiated de novo. The dnaG encoded protein (Primase) was shown to catalyze that function. The purification of the enzyme is reported as well as the characterization of the reactions catalyzed by it.;(2) The discovery by Eisenberg et al. (Eisenberg, S., Scott, J. F., and Kornberg, A.(1976) Proc.Natl.Acad.Sci.U.S.A.73,3151) that a combination of the purified E. coli rep, SSb, as well as the DNA polymerase III elongation system and (phi)X174 A proteins catalyzed net synthesis of (+)SS(c) DNA when (phi)X174 RFI DNA was used as a template, led to their proposal of a two-step model of (phi)X174 RF (---,) RF DNA replication.;I report here that cell-free extracts of thermosensitive E. coli mutants in the dnaB, dnaC, and dnaG gene synthesize and ...
Cancers can be categorized into two groups: those whose frequency increases with age, and those resulting from errors during mammalian development. The first group is linked to DNA replication through the accumulation of genetic mutations that occur during proliferation of developmentally acquired stem cells that give rise to and maintain tissues and organs. These mutations, which result from DNA replication errors as well as environmental insults, fall into two categories; cancer driver mutations that initiate carcinogenesis and genome destabilizing mutations that promote aneuploidy through excess genome duplication and chromatid missegregation. Increased genome instability results in accelerated clonal evolution leading to the appearance of more aggressive clones with increased drug resistance. The second group of cancers, termed germ cell neoplasia, results from the mislocation of pluripotent stem cells during early development. During normal development, pluripotent stem cells that originate in
For cells to proliferate, the genome must be replicated exactly once per cell cycle in a timely and accurate manner. Making this task difficult are multiple other genomic processes, such as transcription and DNA repair, that are concurrently operating on the same genomic template. Replication initiates at specific loci called replication origins that must undergo a series of protein loadings before they can begin to replicate. Although this loading schedule takes place at all origins, individual origins fire at distinct and conserved times during S-phase. It has been suggested that origin firing schedules are defined by their propensity to attract rate limiting replication factors from limited pools (where origins with higher propensities replicate earlier and origins with lower propensities replicate later). This model has not been validated and, furthermore, the factors determining an origins propensity to attract replication factors remains poorly understood. In higher eukaryotes, ...
The replisome is a complex molecular machine that carries out replication of DNA. The replisome first unwinds double stranded DNA into two single strands. For each of the resulting single strands, a new complementary sequence of DNA is synthesized. The net result is formation of two new double stranded DNA sequences that are exact copies of the original double stranded DNA sequence. In terms of structure, the replisome is composed of two replicative polymerase complexes, one of which synthesizes the leading strand, while the other synthesizes the lagging strand. The replisome is composed of a number of proteins including helicase, RFC, PCNA, gyrase/topoisomerase, SSB/RPA, primase, DNA polymerase III, RNAse H, and ligase. For prokaryotes, each dividing nucleoid (region containing genetic material which is not a nucleus) requires two replisomes for bidirectional replication. The two replisomes continue replication at both forks in the middle of the cell. Finally, as the termination site ...
offered the super-Chk1 strain; D.M. element mini-chromosome maintenance (MCM)3 that limiting origin licensing affects the features of hematopoietic stem cells and the differentiation of rapidly-dividing erythrocyte precursors. Mcm3-deficient erythroblasts display aberrant DNA replication patterns and fail to total maturation, causing lethal anemia. Our results indicate that hematopoietic progenitors are particularly sensitive to replication stress, and full source licensing ensures their right differentiation and features. The process of genomic duplication starts at replication origins, which are licensed in the G1 phase of the cell division cycle, several hours before their activation in S phase. The licensing process is definitely led by the origin recognition complex (ORC), cell division cycle 6 (CDC6) and Cdc10-dependent transcript 1 (CDT1) proteins, which cooperate to engage the mini-chromosome maintenance (MCM) complex with the DNA. MCM, made up by essential subunits MCM2-7, displays DNA ...
1. Kotsantis P, Petermann E, Boulton SJ. Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place. Cancer Discov. 2018;8(5):537-55. doi: 10.1158/2159-8290.CD-17-1461 29653955. 2. Gaillard H, García-Muse T, Aguilera A. Replication stress and cancer. Nat Rev Cancer. 2015;15(5):276-89. doi: 10.1038/nrc3916 25907220. 3. Heller R, C., Kang S, Lam W, M., Chen S, Chan C, S., Bell S, P. Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases. Cell. 2011;146(1):80-91. doi: 10.1016/j.cell.2011.06.012 21729781. 4. Sheu YJ, Stillman B. Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell. 2006;24(1):101-13. doi: 10.1016/j.molcel.2006.07.033 17018296. 5. Tanaka S, Nakato R, Katou Y, Shirahige K, Araki H. Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing. Curr Biol. 2011;21(24):2055-63. doi: 10.1016/j.cub.2011.11.038 ...
Proper DNA replication and well-timed cell cycle progression are vital to the normal functioning of a cell. Precise coordination between these mechanisms constituent proteins ensures their processivity while safeguarding against DNA damage. The Ctf4 protein is a central member of the replication fork and links the replicative MCM helicase and polymerase [alpha]-primase. In addition, it has been implicated as a member of a complex that promotes replication fork stability, the Fork Protection Complex (FPC). This investigation represents the first phenotypic analysis of the function of the Ctf4 protein within a multicellular organism model. We show that Ctf4 interacts with Polymerase [alpha], MCM2, Psf1, and Psf2. We also demonstrate that knockdown of this central replication fork component via a GAL4-UAS RNAi system results in a lower frequency of mitosis due to an S-phase delay, endoreplication defects, as well as mitotic bridging in early embryonic development ...
Recombinant Human DNA polymerase eta protein is a Wheat germ Full length protein 1 to 414 aa range and validated in WB, ELISA, SDS-PAGE.
Research Topics, Scientific Experts, Locale, Genomes and Genes, Publications, Species about Experts and Doctors on dna replication in Cincinnati, Ohio, United States
The life cycle of an adenovirus is divided into early and late phases, separated by the DNA replication process. In the early phase, the virus attaches to a cell with its fibers. The penton base protein interacts with the host cell integrins, and the penton is internalized by the host cell through receptor-mediated endocytosis. The penton is disassembled as it is transported to the nucleus, where the viral particle releases its DNA. The viral DNA takes over as terminal protein attached to the end of the DNA strand initiates transcription. The early genes are responsible for making regulatory proteins, which alter the host proteins to prepare for DNA synthesis, activate other virus genes, and provide protection from the hosts immune system. Viral DNA replication now occurs. The late phase begins when the late genes are expressed during DNA replication. These genes produce proteins that are involved in virus particle assembly. The hosts cellular processes are shut down as transport of mRNA to ...
Replication machineries include primosotors are replication enzymes; DNA polymerase, DNA helicases, DNA clamps and DNA ... DNA replication occurs during the S-stage of interphase. DNA replication (DNA amplification) can also be performed in vitro ( ... Fixing of replication machineries as replication factories can improve the success rate of DNA replication. If replication ... "DNA replication , why we have to study DNA replication?". Microb Life. 2020-05-25. Retrieved 2020-05-29. "GENETICS / DNA ...
The mutation rate per base pair per replication during phage T4 DNA synthesis is 1.7 per 108. Termination of DNA replication in ... DNA polymerase III holoenzyme is loaded into the DNA and replication begins. The catalytic mechanism of DNA polymerase III ... The rate of DNA replication in a living cell was first measured as the rate of phage T4 DNA elongation in phage-infected E. ... Prokaryotic DNA Replication is the process by which a prokaryote duplicates its DNA into another copy that is passed on to ...
List of major proteins involved in eukaryotic DNA replication: DNA replication Prokaryotic DNA replication Processivity Leman ... During DNA replication, the replisome will unwind the parental duplex DNA into a two single-stranded DNA template replication ... Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA ... The process of semiconservative replication for the site of DNA replication is a fork-like DNA structure, the replication fork ...
DNA replication control mechanisms cooperate to prevent the relicensing of replication origins and to activate cell cycle and ... Replication of DNA always begins at an origin of replication. In yeast, the origins contain autonomously replicating sequences ... For the special case of cell cycle-regulated DNA replication in which DNA synthesis is uncoupled from cell cycle progression ... Thus, CDKs serve a dual role in the regulation of eukaryotic DNA replication: elevated CDK activity initiates replication at ...
The events that contribute to replication stress occur during DNA replication, and can result in a stalled replication fork. ... The replication fork consists of a group of proteins that influence the activity of DNA replication. In order for the ... DNA interstrand cross-links (ICLs) cause replication stress by blocking replication fork progression. This blockage leads to ... leading to inadequate amounts of DNA replication components. These losses can contribute to the DNA damage response (DDR). ...
... essential replication protein that colocalizes with the origin recognition complex and links DNA replication with mitosis and ... CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the CDT1 gene. It is a ... Nishitani H, Lygerou Z, Nishimoto T, Nurse P (2000). "The Cdt1 protein is required to license DNA for replication in fission ... Overview of all the structural information available in the PDB for UniProt: Q9H211 (Human DNA replication factor Cdt1) at the ...
The process of duplicating DNA is called DNA replication, and it takes place by first unwinding the duplex DNA molecule, ... Another possibility is that the replication timing of a section of DNA contributes to the packaging of that DNA. It has been ... starting at many locations called DNA replication origins, followed by an unzipping process that unwinds the DNA as it is being ... Replication timing refers to the order in which segments of DNA along the length of a chromosome are duplicated. In eukaryotic ...
Cell biology and genomics RNA interference (RNAi) and small-RNA biology; DNA replication; RNA splicing; signal transduction; ... Stillman, B (December 1996). "Cell cycle control of DNA replication". Science. 274 (5293): 1659-64. Bibcode:1996Sci...274.1659S ... Cairns performed important experiments on DNA replication in the bacteria E. coli.[citation needed] James D. Watson served as ... devoted to the study of DNA replication and chromosome maintenance. Stillman is credited with the 1991 discovery and ...
PEAR is a minimal DNA replication system, so it can be considered as a minimal life system. it is of therectical interests to ... The repetitive DNA products can be transferred directly into cells or organisms to study the function of the repetitive DNA. ... Polymerase-endonuclease amplification reaction (PEAR) is a DNA amplification technology for the amplification of ... in which thermostable DNA polymerase elongation and strand slipping generate duplex tandem repeats, and thermostable ...
DNA replication also works by using a DNA template, the DNA double helix unwinds during replication, exposing unpaired bases ... There are several different definitions for DNA synthesis: it can refer to DNA replication - DNA biosynthesis (in vivo DNA ... Control of the DNA replication system ensures that the genome is replicated only once per cycle; over-replication induces DNA ... This damage is in the form of DNA lesions that arise spontaneously or due to DNA damaging agents. DNA replication machinery is ...
It is essential for initiation of DNA replication and separation of spindle pole bodies, hence for the formation of the poles ... The development of B-type cyclin-cyclin-dependent kinase activity, as well as the onset of DNA replication, requires ... DNA replication). Up until now it is not satisfyingly understood how Cdc4 triggers G2-M transition. In general, the second ... and the replication protein Cdc6. In addition to those functions mentioned above, Cdc4 is involved in some other degradation- ...
Griffiths AJ, Gelbart WM, Miller JH, Lewontin RC (1999). "DNA Replication". Modern Genetic Analysis. New York: W. H. Freeman. ... replication, and DNA repair. The entirety of genome function is based on the underlying relationship between nuclear ... and to elements of replication and transcription of mitochondrial DNA, or mtDNA. The second nuclear respiratory factor (NRF-2) ... Mitochondrial DNA is useful in the study of speciation as it tends to be the first to evolve in the development of a new ...
"Differential relationship of DNA replication timing to different forms of human mutation and variation". Am. J. Hum. Genet. ... Replication timing quantitative trait loci (or rtQTL) are genetic variations that lead to a differential use of replication ... "Genetic variation in human DNA replication timing". Cell. 159 (5): 1015-1026. doi:10.1016/j.cell.2014.10.025. PMC 4359889. PMID ... origins, exhibiting allele-specific effects on replication timing. Originally, 16 rtQTL were found in an analysis of human ...
This can either involve the replication of DNA in living organisms such as prokaryotes and eukaryotes, or that of DNA or RNA in ... Although DNA replication is essential for genetic inheritance, defined, site-specific replication origins are technically not a ... Why have metazoan replication origins diverged from the DNA sequence-specific recognition paradigm that determines replication ... DNA replication is divided into different stages. During initiation, the replication machineries - termed replisomes - are ...
The bound Tus protein effectively halts DNA polymerase movement. Tus helps end DNA replication in prokaryotes. In E. coli, Tus ... "Interaction of the Escherichia coli replication terminator protein (Tus) with DNA: a model derived from DNA-binding studies of ... the replication arrest protein of Escherichia coli." "Structure of a replication-terminator protein complexed with DNA." ... "Interaction of the Escherichia coli replication terminator protein (Tus) with DNA: a model derived from DNA-binding studies of ...
Poxvirus is unique from other DNA viruses in respect to its locale of replication in the cell. Poxvirus replicates in the ... Moss, B. (1 September 2013). "Poxvirus DNA Replication". Cold Spring Harbor Perspectives in Biology. 5 (9): a010199. doi: ... Poxvirus starts its replication cycle by attaching to host cell receptors. These receptors are thought to be glycosaminoglycan ... The central region of the genome contains 90-100+ homologous genes that are involved in viral replication, and these genes are ...
DNA has a greater probability of having mutations because it has gone through a higher number of replications as compared to ... "new DNA" likely differentiates into progenitor cell and the other cell carrying "old DNA" likely renews as a stem cell with ... As explained by the immortal DNA strand hypothesis, non-random chromosome segregation has a unique significance in asymmetric ... segregation of chromosomes arises from unequal partitioning of chromosomes according to the age of their template DNA strands. ...
Okazaki R, Okazaki T, Sakabe K, Sugimoto K (June 1967). "Mechanism of DNA replication possible discontinuity of DNA chain ... newly synthesized DNA fragments that are formed on the lagging template strand during DNA replication. They are complementary ... In 1966, Kiwako Sakabe and Reiji Okazaki first showed that DNA replication was a discontinuous process involving fragments. The ... Ogawa T, Okazaki T (1980). "Discontinuous DNA replication". Annual Review of Biochemistry. 49: 421-57. doi:10.1146/ ...
DNA synthesis begins at specific sites called origins of replication. These are regions of the genome where the DNA replication ... "nonfunctional DNA." Junk DNA is often confused with non-coding DNA[citation needed]. The Encyclopedia of DNA Elements (ENCODE) ... A typical replication origin covers about 100-200 base pairs of DNA. Prokaryotes have one origin of replication per chromosome ... Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA ...
One feature of this group is a large genome and the presence of many genes involved in DNA repair, DNA replication, ... These include four key proteins involved in DNA replication and repair: the enzymes DNA polymerase family B, the topoisomerase ... The Poxviridae have a linear double-stranded DNA molecule that can have a length of up to 230 kilobases. The replication of ... Once the virus infects the host, the replication cycle takes place in the cytoplasm. Within the genome, DNA repair enzymes can ...
The factories are also where DNA replication, gene expression, and mature virions (MV) are created. MVs are able to bind to the ... Moss B (September 2013). "Poxvirus DNA replication". Cold Spring Harbor Perspectives in Biology. 5 (9): a010199. doi:10.1101/ ... The outer membrane protects the enzymes, DNA, and transcription factors of the virus. Typical DNA viruses replicate and express ... DNA concatemers process the genomes, which appear in new virions, along with other enzymes, and genetic information needed for ...
It binds the viral origin of replication and recruits DNA polymerase and s/s DNA-binding protein such that once its ... HIV has two stages of protein expression but these are not as a result of two stages of transcription surrounding replication ... The middle T antigen is not required for replication and it acts to enhance transcription by binding host proteins which ... The classification of viral proteins as early proteins or late proteins depends on their relationship with genome replication. ...
Many mechanisms of (-) DNA replication initiation in the SPLCV have been identified but this first step in the replication ... DNA-A typically encodes products for DNA replication, controls gene expression, and controls insect transmission. This suggests ... strand origin of DNA replication. As replication continues, elongation occurs in order to produce dsDNA followed by the ... The presence of DNA primase along with polymerase activity has been noted as one method of replication initiation. During ...
The general categories of function are: Information: storage, maintenance of genetic code; DNA replication and repair; general ... Sequence Search Submit a protein or DNA sequence for SCOP superfamily and family level classification using the SUPERFAMILY ...
Valentine, Ann M.; Ishmael, Faoud T.; Shier, Vincent K.; Benkovic, Stephen J. (2001). "A Zinc Ribbon Protein in DNA Replication ... Benkovic, Stephen J.; Valentine, Ann M.; Salinas, Frank (2001). "Replisome-Mediated DNA Replication". Annual Review of ... and the mechanics of replisome and primase in DNA replication. In 2001, Valentine joined the chemistry faculty of Yale ...
His work defined an origin of DNA replication that led to the development of many suicide cloning vectors still in use today. ... Kolter, R; Helinski, DR (1982). "Plasmid R6K DNA replication. II. Direct nucleotide sequence repeats are required for an active ... Jacob, François; Brenner, Sydney; Cuzin, François (1963-01-01). "On the Regulation of DNA Replication in Bacteria". Cold Spring ... Finkel, S. E.; Kolter, R. (November 2001). "DNA as a nutrient: novel role for bacterial competence gene homologs". Journal of ...
Replication begins once NS1 binds to and makes a nick in a replication origin site in the duplex DNA molecule at the end of one ... required for DNA replication and packaging and act as hinges during replication to change the direction of replication. When ... end of the DNA attached to the capsid. Parvoviruses lack the ability to induce cells into their DNA replication stage, called S ... They have linear, single-stranded DNA (ssDNA) genomes that typically contain two genes encoding for a replication initiator ...
ISBN 978-0-00-220212-1. Possingham, J.V.; Rose, R.J. (May 18, 1976). "Chloroplast Replication and Chloroplast DNA Synthesis in ... ISBN 978-0-300-08295-1. Heinhorst, S.; Cannon, G.C. (January 1993). "DNA Replication in Chloroplasts". Journal of Cell Science ... ISBN 978-1-85996-130-8. Kress, W.J.; Wurdack, K.J.; Zimmer, E.A.; Weigt, L.A.; Janzen, D.H. (June 2005). "Use of DNA Barcodes ... Molecular analysis of DNA sequences from most families of flowering plants enabled the Angiosperm Phylogeny Group to publish in ...
DNA replication, Bacterial genetics). ... replication of the main chromosome begins before replication of ... Bacteria also rely on different replication factors to start replication between the chromosome and the chromid. Replication of ... For this reason, replication of the chromid is delayed to coordinate replication termination between the chromosome and chromid ... On the other hand, chromids do not share the replication systems of chromosomes. Instead, they use the replication system of ...
"Supplement to DNA Replication". San Francisco:Freeman. Henikoff, S.; Keene, M. A.; Sloan, S.; Bleskan, J.; Hards, R.; Patterson ...
Seumahu, C. A.; Suwanto, A.; Rusmana, I.; Solihin, D. D. (2012). "Comparison of DNA Extraction Methods for Microbial Community ... origin of replication, and transfer functions". Journal of Bacteriology. 174 (4): 1124-34. PMC 206405. PMID 1735707. Teo, J. W ... DNA sequence and mechanism of transfer". Journal of Bacteriology. 182 (1): 81-90. doi:10.1128/jb.182.1.81-90.2000. PMC 94243. ...
Replication follows the dsDNA bidirectional replication model. DNA-templated transcription, with some alternative splicing ... Viral replication is nuclear. Entry into the host cell is achieved by attachment of the viral proteins to host receptors, which ...
These complexes then activate S-Cdk complexes that move forward with DNA replication in the S phase. Concurrently, anaphase- ... Reasons the cell would not move into the S phase include insufficient cell growth, damaged DNA, or other preparations have not ... the cell grows in size and synthesizes mRNA and protein that are required for DNA synthesis. Once the required proteins and ...
Replication follows the DNA strand displacement model. DNA-templated transcription is the method of transcription. Bacteria ... Viral replication is cytoplasmic. Entry into the host cell is achieved by adsorption into the host cell. ... Genomes are linear, double stranded DNA, and are relatively small (between 16-20 kbp)-hence the term pico-virinae. Picoviruses ...
Müller K, Mermod N (2000). "The histone-interacting domain of nuclear factor I activates simian virus 40 DNA replication in ... Tarapore P, Richmond C, Zheng G, Cohen SB, Kelder B, Kopchick J, Kruse U, Sippel AE, Colmenares C, Stavnezer E (1997). "DNA ... "DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI". Nucleic Acids Res. 25 (19 ... gene expression is mediated by decreased DNA binding of nuclear factor I proteins which control constitutive TTF-1 expression ...
... including multiple replication origins, general transcription factors, and DNA repair systems. DasSarma's recent research ( ... a mammalian-type single-stranded DNA-binding protein, in a halophilic archaeon". Applied Microbiology and Biotechnology. 98 (4 ...
DNA Cell Biol. 16 (11): 1289-98. doi:10.1089/dna.1997.16.1289. PMID 9407001. Yang X, Khosravi-Far R, Chang HY, Baltimore D ( ... "Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres ... Although it contains no known DNA-binding domains, Daxx can interact and suppress several transcription factors, such as p53, ...
Gurling H, Pimm J, McQuillin A (January 2007). "Replication of genetic association studies between markers at the Epsin 4 gene ... DNA Res. 3 (1): 17-24. doi:10.1093/dnares/3.1.17. PMID 8724849. Hoja MR, Wahlestedt C, Höög C (2000). "A visual intracellular ...
The antiparallel structure of DNA is important in DNA replication because it replicates the leading strand one way and the ... During DNA replication, the leading strand is replicated continuously whereas the lagging strand is replicated in segments ... "Re: Why are the two strands of a DNA molecule antiparallel?". Retrieved 2017-04-06. "why is DNA antiparallel? ... and can be used to define the movement of enzymes such as DNA polymerases relative to the DNA strand in a non-arbitrary manner ...
Replication follows the ssDNA rolling circle model. DNA-templated transcription, with some alternative splicing mechanism is ... Viral replication is nuclear. Entry into the host cell is achieved by penetration into the host cell. ...
This information is protected by DNA repair mechanisms and propagated through DNA replication. Many viruses have an RNA genome ... The two nucleic acids, DNA and RNA, are polymers of nucleotides. Each nucleotide is composed of a phosphate attached to a ... Sierra S, Kupfer B, Kaiser R (December 2005). "Basics of the virology of HIV-1 and its replication". Journal of Clinical ... These biochemicals can be joined to make polymers such as DNA and proteins, essential macromolecules of life. Proteins are made ...
This recombination is crucial to viral replication. DNA exonucleases have roles to play in DNA metabolism, such as: replication ... The function of this protein domain is to digest DNA. Most viruses, inject their host with linear DNA, and this gets ... It is thought that the tapered channel is large enough to accommodate double-stranded DNA at the wide end but only single- ... It has a preference for 5'-phosphorylated DNA ends. It thus forms part of the two-component SynExo viral recombinase functional ...
... genome sizes Human genome Junk DNA List of sequenced eukaryotic genomes Non-coding DNA Plant DNA C-values Database Selfish DNA ... It has been proposed that the small size of RNA viruses is locked into a three-part relation between replication fidelity, ... Some single-celled organisms have much more DNA than humans, for reasons that remain unclear (see non-coding DNA and C-value ... Genome size is the total amount of DNA contained within one copy of a single complete genome. It is typically measured in terms ...
... encoded protein may act as a transcriptional cofactor and be involved in the regulation of DNA transcription and replication. ...
2. DNA ligase During normal DNA replication, DNA ligase catalyzes end-to-end joining (ligation) of short fragments of DNA, ... Recombinant DNAReplication of recombinant DNA within host cell ↓ Isolation, sequencing, and manipulation of purified DNA ... In order for DNA cloning to be completed, it is necessary to obtain discrete, small regions of an organism's DNA that ... The key to cloning a DNA fragment is to link it to a vector DNA molecule that can replicate within a host cell. After a single ...
This is the first dataset related to Monkeypox viral DNA in wastewater in Bangkok. Monkeypox viral DNA was first detected in ... ACAM2000 is not recommended for potentially immunocompromised persons due to high replication competency of vaccinia while ... Diagnosis can be confirmed by testing a lesion for the virus's DNA. There is no known cure. A study in 1988 found that the ... From the first week of July, the number of viral DNA copies increased. Sanger sequencing confirmed the identification of the ...
Moiseeva O, Mallette FA, Mukhopadhyay UK, Moores A, Ferbeyre G (April 2006). "DNA Damage Signaling and p53-dependent Senescence ... Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infections. ... Interferon was scarce and expensive until 1980, when the interferon gene was inserted into bacteria using recombinant DNA ... Inhibited protein synthesis impairs both virus replication and infected host cells. In addition, interferons induce production ...
Protein-Primed Replication of Bacteriophage Φ29 DNA". In Kusic-Tisma, Jelena (ed.). DNA Replication and Related Cellular ... and its own DNA polymerase to synthesize DNA in a 5' to 3' direction. This replication process also employs a sliding-back ... that complexes with DNA polymerase during replication. Φ29 is one of many phages with a DNA polymerase that has a different ... The Φ29 DNA packaging motor packages the phage genome into the procapsid during viral replication. The Φ29 packaging motor is ...
This was the first time that more than a single origin of DNA replication had been shown to be used in a prokaryotic cell. The ... Sulfolobus is now used as a model to study the molecular mechanisms of DNA replication in Archaea. And because the system of ... In 2004, the origins of DNA replication of Sulfolobus solfataricus and Sulfolobus acidocaldarius were identified. It showed ... it was suggested that Archaea could be used as a model to study the much more complex DNA replication in Eukaryota. Sulfolobus ...
Depletion of macro-nutrients and micro-nutrients promotes viral replication that contributes to greater risks of HIV ... "Genital Shedding of Human Immunodeficiency Virus Type 1 DNA during Pregnancy: Association with Immunosuppression, Abnormal ... increases the rate of HIV replication, therefore accelerating the progression of AIDS. AIDS is a disease of the human immune ... worm infections can cause immune activation that increases susceptibility of HIV infection and vulnerability to HIV replication ...
The essential replication system in RK2 consists of an origin of replication, oriV, and a gene, trfA, whose gene product, the ... selfish DNA molecules with a complicated regulatory circuit" RK2 was first isolated in connection with an outbreak of ... PFF1 consists of an origin of replication, oriV, an origin of transfer, oriT, a gene coding for plasmid replication proteins, ... In Escherichia coli, replication proceeds unidirectionally from oriV after activation by TrfA. In E. coli, multiple plasmid ...
Portal: Biology (Protein pages needing a picture, DNA replication, EC 2.7.7, Polymerase chain reaction). ... Vent polymerase is a thermostable archean DNA polymerase used for the polymerase chain reaction. It was isolated from the ... Vigneault F, Drouin R (2005). "Optimal conditions and specific characteristics of Vent exo- DNA polymerase in ligation-mediated ...
Replication follows the dsDNA bidirectional replication model. DNA-templated transcription, with some alternative splicing ... Viral replication is nuclear. Entry into the host cell is achieved by attachment of the viral proteins to host receptors, which ...
... which plays a role in the DNA damage response (DDR) pathway by regulating post replication repair of UV-damaged DNA. It also ... SLF2 is predicted to play a role in the DNA damage response (DDR) pathway by regulating post-replication repair of UV-damaged ... "DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links". Science. 348 (6234): ... Räschle, M., Smeenk, G., Hansen, R. K., Temu, T., Oka, Y., Hein, M. Y., … Mann, M. (2015). DNA repair. Proteomics reveals ...
Replication follows the rolling-hairpin model. DNA-templated transcription, with some alternative splicing mechanism is the ... In Canine minute virus NP1 has been shown to be essential for an early step in viral replication and is also required for the ... Viral replication is nuclear. Entry into the host cell is achieved by attachment to host receptors, which mediates clathrin- ... that is involved in viral genome replication. ORF2 encodes the two capsid proteins-VP1 and VP2. Like other parvoviruses, the ...
"DNA replication" on their own, without adult assistance. He suggested this would lead to "unstoppable learning" through a " ...
Moreover, nuclear DNA genes involved in aerobic respiration and in mitochondrial DNA replication and transcription were either ... Mitochondrial DNA is replicated by the DNA polymerase gamma complex which is composed of a 140 kDa catalytic DNA polymerase ... Mitochondrial DNA is only a small portion of the DNA in a eukaryotic cell; most of the DNA can be found in the cell nucleus and ... one precious model for organelle DNA inheritance and evolution". DNA and Cell Biology. 28 (2): 79-89. doi:10.1089/dna.2008.0807 ...
It is important in maintaining basic cellular functions such as DNA replication, RNA transcription, cell division and cell ...
These adducts and alterations represent lesions which, upon DNA replication cause the insertion of a mis-matched base in the ... This active form then intercalates between DNA base residues and forms adducts with guanine residues, most commonly aflatoxin ... 8-hydroxyguanine lesions and DNA damage. Carcinogenicity The carcinogenicity of aflatoxin B1, which is characterized by the ... "Aflatoxin genotoxicity is associated with a defective DNA damage response bypassing p53 activation". Liver International. 31 (4 ...
... A simple animation showing how dna makes a copy of it self via a process called replication ... You just viewed DNA Replication Animation. Please take a moment to rate this material. ...
Yeast DNA Polymerase & Participates in Leading-Strand DNA Replication. Science, 2007. About the National Institute of ... DNA polymerase epsilon has a primary role in replicating the leading strand of DNA. DNA polymerase epsilon was found to be a ... According to Pursell, a researcher in the DNA Replication Fidelity Group at NIEHS and first author on the paper the studys ... The researchers built on fundamental discoveries on the structure and replication of DNA made by Nobel laureates James Watson, ...
DNA Replication News and Research. RSS DNA replication, the basis for biological inheritance, is a fundamental process ... Hence, following DNA replication, two identical DNA molecules have been produced from a single double-stranded DNA molecule. ... Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication. Further Reading. *DNA ... have analyzed how the protein composition of the DNA replication machinery changes upon encountering damaged DNA. ...
DNA replication initiates locations known as origins. One feature of bacterial origins is an AT-rich sequence known as a DNA ... DnaA is an AAA+ ATPase involved in the initiation of replication. Although it was thought that the energy of ATP hydrolysis was ... In bacteria, the AAA+ domain of the initiator DnaA has been proposed to assist in single-stranded DNA formation during origin ... Although this extension of DNA by a filament is surprisingly similar to the early steps in homologous pairing by RecA protein, ...
video: ,p,This video shows replication of individual pieces of double stranded DNA. This is the first time DNA replication -- ... DNA replication basics The DNA double helix is made from two strands that run in opposite directions. Each strand is made of a ... Failures in DNA replication can lead to cancer, birth defects or other harm *Video shows single pieces of double-helix DNA ... Over time, any one DNA polymerase will move at an average speed; look at a number of DNA polymerases synthesizing DNA strands ...
Home Tools & Resources Video Library DNA Replication with a Proofreading Polymerase DNA Replication with a Proofreading ... Proofreading polymerases have several checkpoints to prevent incorrect nucleotide incorporation during the DNA extension ... Visit for help in selecting the right DNA polymerase for your experiment. ... the polymerase shifts the strand back into the polymerase domain and continues adding bases and extending the DNA.. Fidelity is ...
These DNA components were seen only after heat treatment or after relaxation of the mtDNA with a restrictio … ... exhibited a set of three low molecular weight DNA bands in addition to the major mtDNA band when electrophoresed in ... Heat-treated samples of human mitochondrial DNA (mtDNA) ... Human mitochondrial DNA: analysis of 7S DNA from the origin of ... Heat-treated samples of human mitochondrial DNA (mtDNA) exhibited a set of three low molecular weight DNA bands in addition to ...
To build you, and then keep you alive, the DNA in your cells needs to undergo replication every day to duplicate your ... When replication origins are eliminated from eukaryotes or bacteria, it prevents DNA replication and eventually leads to death ... Why does this lead to faster growth? By using DNA sequencing, we showed that recombination is able to begin DNA replication at ... Our research on DNA replication was carried out in the single-celled organism Haloferax volcanii, which is a member of the ...
involved in regulation of mitotic DNA replication initiation (BSR). Cellular Component. *located in DNA replication ... Associate with replication origins and promotes loading of DNA polymerases onto the origins to initiate chromosomal DNA ... Complex: DPB11-SLD3-SLD2 DNA replication complex Macromolecular complex annotations are imported from the Complex Portal. These ... 2015) Insights into the Initiation of Eukaryotic DNA Replication. Nucleus 6(6):449-54 PMID: 26710261 *SGD Paper ...
DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in Mycobacterium tuberculosis. ...
Well match your inquiry to the person who can best help you. Expect a response within 48 hours. ...
... replication). How information in DNA can be used to make a protein. ... So how does DNA replicate? And this process is called replication. And we covered this in the introduction video as well, but ... And just to be clear, and we talked about this in the introductory video to DNA, DNA is much more than, you know, a handful of ... So what role does this play as we are trying to express the information in this DNA? Well the DNA, especially if were talking ...
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Periodic Reporting for period 3 - IDRE (IMPACT OF DNA REPLICATION ON EPIGENETICS). Reporting period: 2020-05-01 to 2021-10-31 ... We show that a large proportion of chromatin-based processes are profoundly affected by the DNA replication machinery. These ... One of the ways cells control whether genes are turned on or off is by placing epigenetic tags on their DNA molecule. But ... We combine in vivo labelling of newly replicated DNA and mass spectrometry analysis. ...
Proteins required for efficient G1 arrest and longevity when nutrients are limiting include the DNA replication stress response ... Protection from replication stress by growth-inhibitory effects of caloric restriction, osmotic and other stresses may ... Replication stress also likely impacts the longevity of higher eukaryotes, including humans. ... These findings indicate that replication stress is an important determinant of chronological lifespan in budding yeast. ...
Protein kinases required to establish mitosis prevent re-replication of the DNA. As cells exit mitosis, the cell cycle is reset ... This requires the ordered assembly of many proteins at the origins of DNA replication to form a competent, pre-replicative ... allowing the establishment of a new, competent replication state. ... The initiation of DNA replication in eukaryotic cells is a ... The initiation of DNA replication in eukaryotic cells is a highly regulated process that leads to the duplication of the ...
Cells from patients with the hereditary disease xeroderma pigmentosum carry a mutation such that repair replication of DNA is ... Normal skin fibroblasts can repair ultraviolet radiation damage to DNA by inserting new bases into DNA in the form of small ... Patients with xeroderma pigmentosum develop fatal skin cancers when exposed to sunlight, and so the failure of DNA repair in ... and so the failure of DNA repair in the skin must be related to carcinogenesis. ...
A FANCM protein interaction screen reveals a pyrimidine catabolism enzyme required to prevent cell-intrinsic DNA replication ... stress . This movie has been recorded by ICGEB Trieste at At the Intersection of DNA Replication a… ... At the Intersection of DNA Replication and Genome Maintenance: from Mechanisms to Therapy * * Wetenschap ... A FANCM protein interaction screen reveals a pyrimidine catabolism enzyme required to prevent cell-intrinsic DNA replication ...
DNA Replication Proteins - Haemophilus ...
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Here, we describe FORK-seq, a nanopore sequencingmethod to map replication of single DNA molecules at 200 nucleotide ... Thus, FORK-seq reveals the full extent ofcell-to-cell heterogeneity in DNA replication. ... Along pulse-chased replication intermediates from Saccharomycescerevisiae, we can orient replication tracks and reproduce ... Most genome replication mapping methods profile cell populations, maskingcell-to-cell heterogeneity. ...
Structural basis for human mitochondrial DNA replication, repair and antiviral drug toxicity. Add to your list(s) Download to ... Structural basis for human mitochondrial DNA replication, repair and antiviral drug toxicity ...
We show that the human genomes replication program is broadly encoded in DNA and identify 1,617 cis-acting replication timing ... 2021). The genetic architecture of DNA replication timing in human pluripotent stem cells. Nature Communications, 12 (1) https ... Abstract: DNA replication follows a strict spatiotemporal program that intersects with chromatin structure but has a poorly ... The genetic architecture of DNA replication timing in human pluripotent stem cells. ...
This tutorial will help you to understand how nucleotides are added to the leading and lagging strands of DNA. DNA replication ...
Rif1 has many roles in DNA metabolism and regulates the replication timing program. We demonstrate that repression of DNA ... Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila. ... Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila ... Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila ...
Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs. 1986, Pubmed , Xenbase ... Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factor. 1993, Pubmed , Xenbase ... Nuclei act as independent and integrated units of replication in a Xenopus cell-free DNA replication system. 1987, Pubmed , ... The amino-termini of Rb and p130 strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopus in vitro DNA ...
Postdoctoral Fellow - DNA Replication and Repair. City of Hope. Duarte, CA. ID: 7110318 (Ref.No. 10018151). Posted: November 24 ... The Shen laboratory has been focusing on DNA replication/repair pathway components, cancer genetics and epigenetics, and cancer ... graduates or equivalents in the field of biological/medical sciences with ambition for a scientific career and interest in DNA ... and clinical research as an NCI-designated comprehensive cancer center with NCI-funded T32 postdoctoral training program on DNA ...
DNA replication Remove constraint Subject term: DNA replication Subject term Vibrio splendidus Remove constraint Subject term: ... Crassostrea gigas; DNA replication; Vibrio splendidus; cytoplasm; hematopoiesis; hemocytes; immune response; oysters; pathogens ... Stem-like cells with big nuclei and thin cytoplasm were found in the tubules of gill filaments, where DNA synthesis is ac .... ...
"We hope that by mapping this process, others will eventually convert this knowledge into new treatments for DNA replication- ... ORC as Loader of the Rings: Study details ringed structure of ORC in DNA replication. ... leader of the DNA Replication group at MRC London Institute of Medical Sciences and a senior author of the paper. "Instead, it ... has described in exquisite detail the critical first steps of DNA replication, which allows cells to divide and most advanced ...
... is essential for viral DNA replication. Whereas KOS-NA reduced replication of HSV-1 challenge virus in the corneal epithelium ... Efficacy of an HSV-1 Neuro-Attenuated Vaccine in Mice Is Reduced by Preventing Viral DNA Replication. ... Efficacy of an HSV-1 NeuroAttenuated Vaccine in Mice Is Reduced by Preventing Viral DNA Replication. Viruses 2022, 14, 869. ...
  • In this week's issue of Science, researchers from the National Institute of Environmental Health Sciences (NIEHS) and Umeå University in Sweden report an important discovery about a critical new role that an enzyme called DNA polymerase epsilon plays in replicating DNA in higher organisms such as yeast and perhaps even humans. (
  • The researchers used an innovative strategy to demonstrate that in bakers yeast, DNA polymerase epsilon has a primary role in replicating the leading strand of DNA. (
  • DNA polymerase epsilon was found to be a key determinant of genome stability and of cellular responses to DNA damage resulting from exposures to environmental stress. (
  • Dark gaps in the line are single-stranded DNA where one polymerase failed to attach (the fluorescent dye only binds double-stranded DNA). (
  • An enzyme called primase attaches a "primer" to each strand that allows replication to start, then another enzyme called DNA polymerase attaches at the primer and moves along the strand adding new "letters" to form a new double helix. (
  • On one strand - the "leading strand" - the polymerase can move continuously, leaving a trail of new double-stranded DNA behind it. (
  • But on the other, "lagging strand," the polymerase has to move in starts, attaching, producing a short stretch of double stranded DNA, then dropping off and starting again. (
  • With the mispaired base removed, the polymerase shifts the strand back into the polymerase domain and continues adding bases and extending the DNA. (
  • Visit for help in selecting the right DNA polymerase for your experiment. (
  • Studies of Xenopus claspin indicate that it can physically associate with cognate Cdc45, DNA polymerase epsilon, RPA, RFC, and Rad17-RFC on chromatin. (
  • Mutations in RNA polymerase also reduce the toxic effect of RecFOR, providing a further link between DNA replication, transcription and repair. (
  • To investigate it, we attempted to abolish strand-asynchronous replication in cultured human cybrid cells by knocking out the components of the transcription initiation complexes, mitochondrial transcription factor B2 (TFB2M/mtTFB2) and mitochondrial RNA polymerase (POLRMT/mtRNAP). (
  • Uncoiling the DNA, Priming DNA Synthesis, Structure and Function of DNA Polymerase, Synthesizing the Lagging Strand, Repairing Mistakes after Replication. (
  • DNA polymerase starts synthesizing the complementary strand on one side of the fork by adding complementary bases in a 5′ to 3′ direction. (
  • Because DNA polymerase synthesizes only in a 5′ to 3′ direction, the other strand, called the lagging strand, is synthesized as small fragments called Okazaki fragments . (
  • As DNA polymerase travels along the DNA, more positive supercoils are added ahead of the replication fork. (
  • Unlike RNA polymerase, DNA polymerase needs a preexisting 3 ′ -OH to add bases to. (
  • DNA polymerase then makes DNA starting from this RNA primer. (
  • Two molecules of DNA polymerase III bind to the primers on the leading and lagging strands and synthesize new DNA from the 3 ′ hydroxyls (Fig. 4.3). (
  • DNA polymerase III (PolIII) is the major form of DNA polymerase used to replicate bacterial chromosomes and consists of multiple protein subunits (Fig. 4.4). (
  • Proofreading is the primary guardian of DNA polymerase fidelity. (
  • PCR (polymerase chain reaction) is a technique in which cycles of denaturation, annealing with primer, and extension with DNA polymerase, are used to amplify the number of copies of a target DNA sequence by more than 100 times in a few hours. (
  • The DNA polymerase then extends the primer using the provided nucleotides. (
  • PCR was initially carried out manually in incubators of different temperatures for each step until the extraction of DNA polymerase from thermophilic bacteria . (
  • This bacterium lives in the hot springs at 203°F (95°C). The DNA polymerase from T. aquaticus keeps its activity at above 95°C for many hours. (
  • These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase. (
  • It has affinity for viral thymidine kinase and, once phosphorylated, causes DNA chain termination when acted on by DNA polymerase. (
  • POLQ is a DNA polymerase involved in DNA damage response and repair. (
  • however DNA polymerase delta (pol [delta]) carries muc. (
  • 1) an enzyme called Helicase separates the DNA strands2) DNA polymerase adds complementary. (
  • A segment of DNA or RNA that is complementary to a given DNA sequence and that is needed to initiate replication by DNA polymerase. (
  • When DNA replicates, instead of a G opposite what was C, DNA polymerase adds an A (base-pairs with U). (
  • DNA polymerase makes errors in replication for example, inserting a T opposite a G. Most of these errors are repaired by the proofreading function of the replication complex, but some errors escape and become permanent. (
  • This alteration has the same result as a spontaneous deamination: instead of a G, DNA polymerase inserts an A (base-pairs with U). (
  • Ionizing radiation (X rays) produces highly reactive chemical species called free radicals, which can change bases in DNA to unrecognizable (by DNA polymerase) forms or break the sugar-phosphate backbone causing chromosoma l abnormalities. (
  • polymerase involved, and this in- macromolecules including DNA, 2012) . (
  • Polymerase theta (POLQ) is a DNA repair enzyme that is selectively upregulated and highly active in many types of cancers. (
  • Common DNA recognition strategies of AAA+ proteins. (
  • This requires the ordered assembly of many proteins at the origins of DNA replication to form a competent, pre-replicative chromosomal state. (
  • Two independent cDNAs resulting from this screen were found to encode the carboxy-terminal 137 amino acids of MCM7 , a member of a family of proteins that comprise replication licensing factor. (
  • These data provide the first evidence that Rb and Rb-related proteins can directly regulate DNA replication and that components of licensing factor are targets of the products of tumor suppressor genes. (
  • The role of MCM/P1 proteins in the licensing of DNA replication. (
  • Mcm2-7 (MCM) proteins are part of the origin licensing machinery that regulates initiation of DNA replication. (
  • We have used the degron strains to show that these proteins are required for the establishment and normal progression of DNA replication forks. (
  • FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination . (
  • The protein produced from this gene is one of a group of proteins known as the pre-replication complex. (
  • DNA replication proteins are novel targets for radiosensitizers. (
  • Precise coordination between these mechanisms' constituent proteins ensures their processivity while safeguarding against DNA damage. (
  • Eukaryotic DNA replication is controlled by a number of proteins that ensures the process takes place accurately. (
  • Multiple proteins are involved in the complete and accurate replication of the genome during S phase of the cell cycle. (
  • Bacterial rep proteins, a single-stranded DNA-dependent ATPase involved in DNA replication which can initiate unwinding at a nick in the DNA. (
  • Fungal srs2 proteins, an ATP-dependent DNA helicase involved in DNA repair. (
  • These results suggest that human 7S mtDNA synthesis is terminated at a distinct position and that it is either initiated at one of three possible sites in the same mtDNA or that the mtDNA population consists of three subpopulations, each differing from the others by the presence or absence of a nucleotide sequence immediately adjacent to the origin of replication. (
  • Cells from most XP patients are deficient in repairing DNA damaged by ultraviolet (UV) light as shown by a reduced rate of tritiated thymidine (3HTdR) incorporation during their DNA repair synthesis. (
  • As RPA is not required for claspin binding, it is postulated that claspin binds at the time of initial origin unwinding but prior to the initiation of DNA synthesis. (
  • One is assigned to leading-strand synthesis in the absence of synchronous lagging-strand synthesis (strand-asynchronous replication), and the other has properties of coupled leading- and lagging-strand synthesis (strand-coupled replication). (
  • Our data demonstrate a striking sexual dimorphism in the mechanisms repressing origin licensing and preventing untimely DNA synthesis during meiosis I, implicating a pivotal role for Geminin in maintaining integrity of the male germline genome. (
  • Classic antimetabolite anticancer drug with chemical structure similar to endogenous intermediates or building blocks of DNA or RNA synthesis. (
  • 5-FU inhibits tumor cell growth through at least 3 different mechanisms that ultimately disrupt DNA synthesis or cellular viability. (
  • 5-FdUMP inhibits thymidylate synthase (key enzyme in DNA synthesis), which leads to accumulation of dUMP, which then gets misincorporated into the DNA in the form of 5-FdUTP resulting in inhibition of DNA synthesis and function with cytotoxic DNA strand breaks. (
  • This step interferes with DNA and to a lesser degree with RNA synthesis. (
  • Trifluridine is a thymidine-based nucleoside analog that incorporates into DNA, interferes with DNA synthesis, and inhibits cell proliferation. (
  • These agents inhibit DNA synthesis and viral replication. (
  • A comparison of the level of DNA excision repair (repair replication and unscheduled DNA synthesis) confirms that some forms of alkylating- agent damage (probably mono-filar DNA adducts) are less completely removed by both normal and malignant rodent cells than by their human counterparts, rendering rodent cells more susceptible to the toxic potential of unexcised lesions. (
  • Most mutations are point mutations in which one nucleotide is substituted for another during the synthesis of a new DNA strand. (
  • Duderstadt, K. E. & Berger, J. M. AAA+ ATPases in the initiation of DNA replication. (
  • The initiation of DNA replication in eukaryotic cells is a highly regulated process that leads to the duplication of the genetic information for the next cell generation. (
  • Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs. (
  • Degradation of the CtrA response regulator normally coincides with initiation of DNA replication, but in strains lacking SsrA activity there is a 40-min delay between the degradation of CtrA and replication initiation. (
  • In addition to dedicated duplex-DNA-binding domains, cellular initiators possess AAA+ (ATPases associated with various cellular activities) elements that drive functions ranging from protein assembly to origin recognition. (
  • Fuller, R. S., Funnell, B. E. & Kornberg, A. The dnaA protein complex with the E. coli chromosomal replication origin ( oriC ) and other DNA sites. (
  • Protein kinases required to establish mitosis prevent re-replication of the DNA. (
  • In Drosophila polyploid cells, the SNF2-domain-containing SUUR protein inhibits replication fork progression within specific regions of the genome to promote DNA underreplication. (
  • Our findings uncover an unrecognized function of the Rif1 protein as a regulator of replication fork progression. (
  • Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7 . (
  • Sequence of cDNA comprising the human pur gene and sequence-specific single-stranded-DNA-binding properties of the encoded protein. (
  • Results of the study are published in the journal Nature Structural and Molecular Biology and reveal that a ring-shaped protein called origin recognition complex (ORC) possesses a special alpha-helix, which slips into a groove on DNA and initiates a cascade of microscopic interactions that copy DNA. (
  • At the outset, the six-protein ORCs assemble into a crescent, which envelops the DNA duplex. (
  • The ORCs then recruit a seventh protein, called Cdc6, to encircle DNA. (
  • Next, this ring threads the second ring, called minichromosome maintenance protein (Cdt1-bound Mcm2-7 hexamer), around DNA, which completes loading of the first Mcm2-7 hexamer. (
  • Because KOS-NA contains a neuro-attenuating mutation in a single gene, we sought to improve its safety by deleting a portion of the UL29 gene whose protein product, ICP8, is essential for viral DNA replication. (
  • Claspin would then continue to associate with replication fork machinery where it can serve as a checkpoint sensor protein. (
  • The protein is hypothesized to encircle the DNA at these sites. (
  • PriA protein provides a means to load the DnaB replicative helicase at DNA replication fork and D loop structures, and is therefore a key factor in the rescue of stalled or broken forks and subsequent replication restart. (
  • We show that the nucleoid-associated RdgC protein binds non-specifically to single-stranded (ss) DNA and double-stranded DNA. (
  • The initiating events in the DDR entail both DNA lesion recognition and assembly of protein complexes at the damaged DNA sites. (
  • The CDT1 gene provides instructions for making a protein that is important in the copying of a cell's DNA before the cell divides (a process known as DNA replication). (
  • Interferon alfa-2a and -2b are protein products manufactured by recombinant DNA technology. (
  • Download DNA or protein sequence, view genomic context and coordinates. (
  • GINS a hetero-tetrameric protein complex is known to be essential for the initiation and progression of eukaryotic DNA replication. (
  • Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. (
  • NAD+ is a primary regulator of DNA repair protein-to-protein interactions. (
  • 2007. DNA binding, annealing, and strand exchange activities of Brh2 protein from Ustilago maydis. . (
  • 2007. Ortholog of BRCA2-interacting protein BCCIP controls morphogenetic responses during DNA replication stress in Ustilago maydis. . (
  • 2003. The BRCA2-interacting protein DSS1 is vital for DNA repair, recombination, and genome stability in Ustilago maydis. . (
  • When Watson and Crick first described the structure of DNA in 1953, they pointed out that the two DNA strands, which are referred to as leading and lagging, pair with each other to form the now familiar double helix. (
  • Using sophisticated imaging technology and a great deal of patience, the researchers were able to watch DNA from E. coli bacteria as it replicated and measure how fast enzyme machinery worked on the different strands. (
  • The DNA double helix is made from two strands that run in opposite directions. (
  • The first step in replication is an enzyme called helicase that unwinds and "unzips" the double helix into two single strands. (
  • They could switch replication on by adding chemical fuel (nucleoside triphosphates, NTPs) and used a fluorescent dye that attaches to double-stranded DNA to light up the growing strands. (
  • Finally, the whole set up is in a flow chamber, so the DNA strands stretch out like banners in the breeze. (
  • Once Graham, Marians and Kowalczykowski started watching individual DNA strands, they noticed something unexpected. (
  • And then you would have two strands, two identical strands of the DNA. (
  • Once the replication fork is established, a large assembly of enzymes and factors assembles to synthesize the complementary strands of DNA (see Fig. 4.1). (
  • DNA helicase and DNA gyrase attach near the replication fork and untwist the strands of DNA. (
  • This prevents the two strands from reannealing, so that other enzymes can gain access to the origin and begin replication. (
  • During this process, two strands of the targeted DNA are separated from each other. (
  • This technique, previously developed by the same researchers, lets you examine whether DNA methylation is symmetric across complementary strands at CpGs, therefore allowing for some detailed stem cell division methylation dynamics . (
  • The DNA strands unwind and separate. (
  • When DNA is replicated, the two strands that make up the double helix are separated, and each strand is used as a template to synthesize a new double helix. (
  • If that did happen, it would create stretches of single-stranded DNA that are highly susceptible to damaging mutations. (
  • Many cancer cells have mutations in the genes that control DNA replication, and multiply genome copies are a common feature of cancer cells. (
  • Mutations in the pre-replication complex cause Meier-Gorlin syndrome. (
  • Genetic engineered heat resistant DNA polymerases, that have proofreading functions and make fewer mutations in the amplified DNA products, are available commercially. (
  • The majority is due to 'bad luck,' that is, random mutations arising during DNA replication in normal, noncancerous stem cells. (
  • Induced mutations occur when some agent outside the cell-a mutagen-causes a permanent change in DNA. (
  • More than 2,500 tumour genomes of 36 types of cancer were analysed and the team found DNA mutations pointing to one of the two known mechanisms to lengthen telomeres in 13 of the cases . (
  • BRCA gene mutations) or in combination with inhibitors of the DNA repair enzyme called PARP, DNA gaps accumulated, leading to cancer cell death. (
  • May play an active role in assembly or activation of the replication fork CMG helicase (CPX-297) thus playing a role in a critical S phase regulatory mechanism that restricts DNA replication to S phase. (
  • Biologists have known for many years that both ORC and helicase are ring-shaped structures essential in the initiation and execution of DNA replication, but until now we never understood exactly how the ORC ring loads the helicase ring onto DNA. (
  • The work also reveals that ORC, with the help of Cdc6 and Cdt1, loads the helicase core onto DNA via paired interactions of the so-called winged helix domains. (
  • DNA gyrase removes the supercoiling, and helicase unwinds the double helix by dissolving the hydrogen bonds between the paired bases. (
  • Gram-positive bacterial pcrA helicase, an essential enzyme involved in DNA repair and rolling circle replication. (
  • We identify pluripotency-related transcription factors and boundary elements as positive and negative regulators of replication timing, respectively. (
  • Taken together, human replication timing is controlled by a multi-layered mechanism with dozens of effectors working combinatorially and following principles analogous to transcription regulation. (
  • While strand-asynchronous replication is primed by long noncoding RNA synthesized from a defined transcription initiation site, little is known about the commencement of strand-coupled replication. (
  • The access of Transcription Factors (TFs) to their cognate DNA binding motifs requires a precise control over nucleosome positioning. (
  • It inhibits DNA replication and transcription. (
  • Through transcription the information contained in a section of DNA is replicated to form a new piece of messenger RNA (mRNA). (
  • Researchers at USC have developed a yeast model to study a gene mutation that disrupts the duplication of DNA, causing massive damage to a cell's chromosomes, while somehow allowing the cell to continue dividing. (
  • To build you, and then keep you alive, the DNA in your cells needs to undergo replication every day to duplicate your chromosomes before cell division. (
  • IMSEAR at SEARO: DNA replication in polytene chromosomes of Drosophila pseudoobscura: new facts & their implications. (
  • How the ends of chromosomes, called "telomeres", contribute to maintaining DNA health. (
  • For example, the two polymerases involved in replication (one for each strand) aren't coordinated. (
  • Proofreading polymerases have several checkpoints to prevent incorrect nucleotide incorporation during the DNA extension process. (
  • Associate with replication origins and promotes loading of DNA polymerases onto the origins to initiate chromosomal DNA replication when cyclin-dependent kinase activity increases at the G1/S cell cycle boundary. (
  • This step is followed by RPA binding which is a prerequisite for recruitment of PCNA and DNA polymerases alpha and delta. (
  • New work has revealed that polymerases with intrinsic proofreading activity may cooperate with non-proofreading polymerases to ensure faithful DNA replication. (
  • Several additional heat-resistant DNA polymerases have also now been identified. (
  • A Chinese team reports a correlation between serum levels of microRNA-181b and hepatitis B virus replication and disease progression in patients with chronic HBV infection. (
  • Rif1 localizes to active replication forks in a partially SUUR-dependent manner and directly regulates replication fork progression. (
  • Importantly, SUUR associates with replication forks in the absence of Rif1, indicating that Rif1 acts downstream of SUUR to inhibit fork progression. (
  • It is also essential for growth of a strain lacking PriA, indicating that it might affect replication fork progression or fork rescue. (
  • By screening the collection for defects in cell-cycle progression, here we identify three DNA replication factors that interact with each other and that have uncharacterized homologues in human cells. (
  • Genomic instability is characterized by an elevated propensity of alterations in the genome throughout the cell cycle, where coordinated cell cycle progression and error-free repair of DNA damage are crucial for maintaining genomic integrity. (
  • Proper DNA replication and well-timed cell cycle progression are vital to the normal functioning of a cell. (
  • In bacteria, the AAA+ domain of the initiator DnaA has been proposed to assist in single-stranded DNA formation during origin melting. (
  • Here we show crystallographically and in solution that the ATP-dependent assembly of Aquifex aeolicus DnaA into a spiral oligomer creates a continuous surface that allows successive AAA+ domains to bind and extend single-stranded DNA segments. (
  • This shows up as a dark area in the glowing strand, because the dye doesn't stick to single-stranded DNA. (
  • The three components were single stranded and had sizes of 550, 585, and 629 nucleotides, close to the size (600 nucleotides) estimated from contour length measurements for the 7S DNA from the D loop of human mtDNA. (
  • Interaction of the complex with with single-stranded DNA may be important for GINS attachment to MCM. (
  • The HeLa Pur factor binds single-stranded DNA at a specific element conserved in gene flanking regions and origins of DNA replication. (
  • single-stranded DNA. (
  • It unwinds DNA duplexes with 3'-5' polarity with respect to the bound strand and initiates unwinding most effectively when a single-stranded region is present. (
  • It binds to the single-stranded DNA and acts in a progressive fashion along the DNA in the 3' to 5' direction. (
  • Cdc6 and Cdt1 play an essential role in DNA replication initiation by loading the Mcm2-7 complex, which is required for unwinding the DNA helix, onto chromosomal origins. (
  • This includes arranging the DNA into proper chromosomal structures, ensuring the DNA is accurately replicated each time the cell divides, scanning DNA for damage, and when necessary promoting DNA repair. (
  • This process is "semiconservative" in that each strand of the original double-stranded DNA molecule serves as template for the reproduction of the complementary strand. (
  • Hence, following DNA replication, two identical DNA molecules have been produced from a single double-stranded DNA molecule. (
  • Now for the first time scientists have been able to watch individual steps in the replication of a single DNA molecule, with some surprising findings. (
  • The DNA molecule can be tens of millions of base pairs long. (
  • So for example this might be a section of a much longer molecule, so the much longer strand of DNA, and even there I'm probably not giving justice to it. (
  • One of the ways cells control whether genes are turned 'on' or 'off' is by placing epigenetic tags on their DNA molecule. (
  • FORK-seq: Single-Molecule Profiling of DNA Replication. (
  • Home / Teams / Physical Biology of Chromatin - D. Jost / Publications / FORK-seq: Single-Molecule Profiling of DNA Replication. (
  • The DNA molecule is made up of two long polymers connected by the bonding of hydrogen atoms and coiled. (
  • Deoxyribonucleic acid (DNA) is a complex molecule of many components. (
  • This video will describe how these four groups build upon each other to create the DNA molecule. (
  • The process by which a DNA molecule is duplicated. (
  • In our paper we suggest that replication origins in H. volcanii are an example of a selfish gene. (
  • Even for gene creatures such as plasmids, viruses, or transposons, replication is critical for their survival. (
  • Max Ludwig Henning Delbrick applied his knowledge of theoretical physics to biological systems such as bacterial viruses called bacteriophages, or phages, and gene replication during the twentieth century in Germany and the US. (
  • DNA tumor viruses : control of gene expression and replication / edited by Michael Botchan, Terri Grodzicker, Phillip A. Sharp. (
  • The discovery that xeroderma pigmentosum was a sun-sensitive hereditary human disease that was deficient in DNA repair was made when research into the fundamental mechanisms of nucleotide excision repair was in its infancy and established DNA repair as a central factor for maintaining genomic stability and preventing cancer, neurodegenerative disease and aging. (
  • Here, we describe FORK-seq, a nanopore sequencingmethod to map replication of single DNA molecules at 200 nucleotide resolutionusing a nanopore current interpretation tool allowing the quantification of BrdUincorporation. (
  • The basic-level eLearning course provides information on the fundamental characteristics of DNA and RNA, nucleotide base-pairing rules, and the basic techniques and workflow applied in molecular diagnostics. (
  • The four nucleotide bases of DNA are somewhat unstable. (
  • The Shen laboratory has been focusing on DNA replication/repair pathway components, cancer genetics and epigenetics, and cancer etiological and therapeutics modeling. (
  • Here, we have analysed these replication licensing factors (RLFs) to determine whether the pathway becomes deregulated during mammary carcinogenesis, and have assessed their potential value as prognostic markers. (
  • This uncoupling of initiation of replication from CtrA degradation indicates that there is an SsrA-dependent pathway required for correct timing of DNA replication. (
  • We identified that nuclear actin polymerization alters nuclear architecture and promotes replication stress repair and characterized the regulatory pathway. (
  • Our studies of telomere biology and DNA replication led us unexpectedly to identify how lethal replication stress induces cell death specifically during mitosis through a pathway of cohesion fatigue and non-canonical telomere deprotection. (
  • Alternative lengthening of telomeres (ALT) cancers achieve immortality by reelongating their telomeres in the G2 and M phases of the cell cycle through a specialized break-induced replication (BIR) pathway (1, 2). (
  • Abstract: DNA replication follows a strict spatiotemporal program that intersects with chromatin structure but has a poorly understood genetic basis. (
  • Replication starts at a specific site called an origin of replication (ori) on the chromosome. (
  • We initiated the cloning strategy by creating an E. coli -yeast- Aspergillus shuttle vector, pYH-wA-pyrG, which consists of a ColE1 origin of replication from SuperCos1, a yeast centromere sequence (CEN) and an autonomously replicating sequence (ARS) 13 , 14 ( Table S1, Materials and Methods ). (
  • Researchers have uncovered a new molecular mechanism whereby human cells protect their genome from the detrimental effect of UV radiation and govern DNA replication in cellular mitosis, which, when it malfunctions, leads to harmful results. (
  • As cells exit mitosis, the cell cycle is reset, allowing the establishment of a new, competent replication state. (
  • This is especially important following DNA replication and during mitosis, both resulting in profound changes in nucleosome organization over TF binding regions. (
  • Using mouse Embryonic Stem (ES) cells, we show that the TF CTCF displaces nucleosomes from its binding site and locally organizes large and phased nucleosomal arrays, not only in interphase steady-state but also immediately after replication and during mitosis. (
  • Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication. (
  • We chose H. volcanii because the enzymes that carry out DNA replication in archaea are similar to, but less complex than, those used in multi-cellular organisms. (
  • Li, JJ & Kelly, TJ 1985, ' Simian virus 40 DNA replication in vitro: Specificity of initiation and evidence for bidirectional replication ', Molecular and cellular biology , vol. 5, no. 6, pp. 1238-1246. (
  • To counteract the deleterious effects exerted by DNA lesions, eukaryotic cells have evolved a network of cellular pathways, termed DNA damage response (DDR). (
  • The DDR comprises both mechanisms devoted to repair DNA lesions and signal transduction pathways that sense DNA damage and transduce this information to specific cellular targets. (
  • These targets, in turn, impact a wide range of cellular processes including DNA replication, DNA repair and cell cycle transitions. (
  • RNA is similar in structure to DNA but is involved in different cellular functions. (
  • Studies of purified human claspin indicate that it binds with high affinity to branched (or forked) DNA structures that resemble stalled replication forks. (
  • We suggest that binding of RdgC to DNA limits RecA loading, avoiding problems at replication forks that would otherwise require PriA to promote replication restart. (
  • The amino-termini of Rb and p130 strongly inhibited DNA replication in an MCM7 -dependent fashion in a Xenopus in vitro DNA replication assay system. (
  • To systematically identify genetic regulators of replication timing, we exploited inter-individual variation in human pluripotent stem cells from 349 individuals. (
  • Fanconi anaemia ( FA ) is a rare genetic disease resulting in impaired response to DNA damage. (
  • [2] Because of the genetic defect in DNA repair, cells from people with FA are sensitive to drugs that treat cancer by DNA crosslinking , such as mitomycin C . The typical age of death was 30 years in 2000. (
  • These changes and markers of genetic instability are driven by a failure of DNA repair systems and cell cycle regulation. (
  • DNA is the genetic material for all living organisms which is constantly being unpackaged replicated and repackaged. (
  • Others result from mobile genetic elements snippets of DNA that are able to move between bacteria. (
  • But yet in this marvelous machine occasional errors crop up, inconsistencies in the genetic replication process. (
  • Those dealing with mechanisms of toxicity and carcinogenicity urged more studies on promotion of carcinogenesis and replication of genetic material, somatic mutation rate studies, quantification of somatic mutation rates, and measures of accumulations of DNA adducts and DNA damage. (
  • GRAND RAPIDS, Mich. (Feb. 21, 2017)-An international collaboration of life scientists, including experts at Van Andel Research Institute , has described in exquisite detail the critical first steps of DNA replication, which allows cells to divide and most advanced life, including human, to propagate. (
  • Thus, FORK-seq reveals the full extent ofcell-to-cell heterogeneity in DNA replication. (
  • Even though associated with the replication fork, claspin is not an essential DNA replication factor. (
  • This Y-shaped region of DNA is the replication fork (Fig. 4.1). (
  • We show that a large proportion of chromatin-based processes are profoundly affected by the DNA replication machinery. (
  • Research in our lab continues to study how nuclear and chromatin architecture is regulated during DNA replication to promote genome stability. (
  • Almost all life on earth is based on DNA being copied, or replicated, and understanding how this process works could lead to a wide range of discoveries in biology and medicine. (
  • Recent Ph.D. graduates or equivalents in the field of biological/medical sciences with ambition for a scientific career and interest in DNA repair and cancer biology and skills in molecular biology are encouraged to apply. (
  • Ambition and interest in DNA repair and cancer biology. (
  • Control of DNA copy number is essential to maintain genome stability and ensure proper cell and tissue function. (
  • 2002. BRCA2 homolog required for proficiency in DNA repair, recombination, and genome stability in Ustilago maydis. . (
  • The classic examples of necessarily be processed by the cel replication fidelity can confer strong chemical agents that require met- into a mutation (see Chapter 12, by mutator phenotypes that result in ge- abolic activation to become carci- DeMarini). (
  • Claspin is loaded onto DNA replication origins during replication initiation. (
  • Along pulse-chased replication intermediates from Saccharomycescerevisiae, we can orient replication tracks and reproduce population-basedreplication directionality profiles. (
  • Two classes of replication intermediates have been observed from mitochondrial DNA (mtDNA) in many mammalian tissue and cells with two-dimensional agarose gel electrophoresis. (
  • Recombination is a form of DNA repair, it is normally used to mend breaks in the chromosome. (
  • Normal skin fibroblasts can repair ultraviolet radiation damage to DNA by inserting new bases into DNA in the form of small patches. (
  • Cells from patients with the hereditary disease xeroderma pigmentosum carry a mutation such that repair replication of DNA is either absent or much reduced in comparison to normal fibroblasts. (
  • Patients with xeroderma pigmentosum develop fatal skin cancers when exposed to sunlight, and so the failure of DNA repair in the skin must be related to carcinogenesis. (
  • DNA repair and radiation sensitivity in human (xeroderma pigmentosum) cells. (
  • The results demonstrate the importance of repair replication in the survival of irradiated mammalian cells and in the aetiology of xeroderma pigmentosum. (
  • Relationship of DNA repair to carcinogenesis in xeroderma pigmentosum. (
  • Radioautograms of intact ultraviolet (UV)-irradiated epidermis from a patient with xeroderma pigmentosum showed no detectable abnormality in UV-induced thymidine- 3 H incorporation, suggesting that some mechanism other than enhancement of UV carcinogenesis by defective DNA repair may be responsible for skin tumor formation in this patient. (
  • Direct measurement of the amounts of two products formed by alkylating carcinogens in the DNA and of the rate at which they are eliminated indicates that XP cells have a defect in this type of repair also. (
  • Using the dark repair mechanism in microorganisms as a model, evidence has been presented that XP cells are defective in the incision step of DNA repair3-5. (
  • Very little is known about the details of biochemical events involved in repair of DNA damage in human cells, but genes involved in several of the various repair pathways have been cloned. (
  • These genes are involved in DNA repair. (
  • Enhanced radioresistance is through a prolonged G2/M phase and faster repair of DNA damage, leading to reduced radiation-induced apoptosis. (
  • 4. Induces epigenetic alterations usual y arises as the cell attempts to repair the DNA damage. (
  • Scientists at the Francis Crick Institute, in collaboration with Artios, have identified how an enzyme involved in DNA repair (POLQ), becomes vital to the survival of certain cancers, if the cancer cells lose the ability to use a more common method of DNA repair. (
  • Many cancers become reliant on POLQ to repair DNA damage, a key response important for tumor survival. (
  • There are several types of DNA repair mechanisms that are designed to repair these errors so that replication can continue normally. (
  • They found that POLQ provides a vital repair mechanism in cancer cells unable to repair DNA gaps using a common method called homologous recombination. (
  • Ondrej Belan, first author and postdoctoral researcher at the Crick, said, 'While it is known that blocking POLQ and homologous recombination at the same time hinders DNA repair, our research now provides the scientific foundation to explain how. (
  • The DNA repair process by POLQ is prone to errors which introduces variations in the DNA of cancer cells. (
  • DNA Repair - Presently, scientists don't know why there's a reduction in DNA repairs with age. (
  • DNA repair is an essential factor for cancer prevention and cell survival. (
  • 1998), Negative regulation of DNA replication by the r. (
  • Niida H, Kitagawa M. Regulation of DNA replication licensing. (
  • Is the Subject Area "DNA damage" applicable to this article? (
  • City of Hope offers an unparalleled postdoctoral training environment in basic, translational, and clinical research as an NCI-designated comprehensive cancer center with NCI-funded T32 postdoctoral training program on DNA damage responses and oncogenic signaling. (
  • UVGI that penetrates to microbial DNA may cause damage sufficient to interrupt cell replication. (
  • The relationships between DNA damage from UV radiation, alkylating drugs and the methylated xanthines (MX) have been studied in normal and malignant rodent and human cells. (
  • The toxicity of alkylating agents canbe increased by the presence of several MXs during the period of DNA replication which follows infliction of the damage. (
  • Human cells appear capable of excising more DNA damage, rendering them somewhat less susceptible to enhancement of cytotoxicity by MX. (
  • The most likely mechanism by which MX sensitization is achieved is reversal of the inhibition of DNA replicon initiation which follows the infliction of significant DNA damage. (
  • Whatever the source of this differential activity, it seems likely to involve the exposure of the cell to DNA damage during S phase. (
  • Examples of direct-acting elec- all have an impact on the outcome trophilic carcinogens are formalde- The term "genotoxic" refers to an of this proces s (Arana and Kunkel, hyde, sulfur mustard, and ethylene agent that induces DNA damage, 2010) . (
  • Thus, carcinogens nogenic are polycyclic aromatic hy- to induce DNA damage, it can be may act not only by producing DNA drocarbons and benzene, which by cal ed a genotoxicant or a genotox- damage directly but also by altering themselves are relatively inert chem- in, and if it is shown that the agent the processes that control normal ical y. (
  • PRV promoted NDRG1 expression through DNA damage-induced P53 activation, which was beneficial to viral proliferation. (
  • We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage. (
  • Well, artificially constructing biological DNA could lead to the alteration of abnormal, or malice genes. (
  • Most of the complex creatures living on Earth have more DNA, and therefore more genes, than the simpler creatures do. (
  • Dr. Tumpey says, "The HA and PB1 virus genes of the 1918 virus are essential for maximum replication and virulence. (
  • The four base pairs of DNA are adenine(A),thymine(T),guanine(G) & cytosine(C).They pair up in the. (
  • the most common lesion is a dimer formed by the covalent bonding of 2 nearby thymine bases in one DNA strand. (
  • Ultraviolet radiation from the sun (or a tanning lamp) is absorbed by thymine in DNA, causing it to form interbase covalent bonds with adjacent nucleotides. (
  • Heat-treated samples of human mitochondrial DNA (mtDNA) exhibited a set of three low molecular weight DNA bands in addition to the major mtDNA band when electrophoresed in polyacrylamide gels. (
  • As the replication machinery rolls around the circle, the tail gets longer. (
  • In this case, the origin has hijacked the DNA replication machinery to ensure their own survival. (
  • These findings, combined with strand-displacement assays, indicate that DnaA opens replication origins by a direct ATP-dependent stretching mechanism. (
  • The unusual mechanism of DNA replication we have discovered in H. volcanii has parallels with cancer. (
  • This movie has been recorded by ICGEB Trieste at 'At the Intersection of DNA Replication and Genome Maintenance: 2016 - from Mechanism to Therapy' conference. (
  • The complementary two-stranded structure of DNA is the key to understanding how it is duplicated during cell division. (
  • We combine in vivo labelling of newly replicated DNA and mass spectrometry analysis. (
  • Current therapeutic interventions can only suppress hepatitis B virus (HBV) replication or reduce complications without a cure. (
  • Because DNA is condensed into supercoils in order to fit inside the cell, several different enzymes are needed to open and relax the DNA before replication can start (Fig. 4.2). (
  • Each glowing strand is a piece of double helix growing by replication at the left-hand end. (
  • Basically DNA has a double Helix shape. (
  • This accelerated growth is reminiscent of originless H. volcanii , which use alternative mechanisms of replication to outpace other cells. (
  • The cell begins as a immensely complex machine with a multitude of interdependent processes and not a strand of DNA. (
  • We can't discuss the evolutionary processes without first discussing Deoxyribonucleic acid, better known as DNA. (
  • RecBCD is a multi-functional enzyme complex that processes DNA ends resulting from a double-strand break. (
  • Any fragments present in two copies must have been duplicated, and will point to the location of replication origins. (
  • Zegerman P and Diffley JF (2007) Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. (
  • The study was conducted on the DNA of Saccharomyces cerevisiae , better known as baker's yeast, because of its biological and genomic similarity to larger organisms, including mammals, at an average resolution of 3.9 Angströms (about 40 billionths of a meter), which is roughly the diameter of a single atom of sodium. (
  • Kaguni, J. M. DnaA: controlling the initiation of bacterial DNA replication and more. (
  • Because the bacterial chromosome is negatively supercoiled, initially the new positive supercoils relax the DNA. (
  • The labs develop and compare DNA patterns from bacterial pathogens submitted by state, Food and Drug Administration, and the U.S. Department of Agriculture laboratories from across the nation. (
  • The work of PulseNet provides insight into the lives of a bacterial cell through DNA pattern matches. (
  • SN-38 binds to and stabilizes the topoisomerase I-DNA complex and prevents the relegation of DNA after it has been cleaved by topoisomerase I, inhibiting DNA replication. (
  • Inhibition of DNA replication factor RPA by p53. (
  • DNA replication, the basis for biological inheritance, is a fundamental process occurring in all living organisms to copy their DNA. (
  • Many replication initiators form higher-order oligomers that process host replication origins to promote replisome formation. (
  • This is the first time DNA replication -- arguably, the fundamental process of life on Earth -- has been observed directly. (
  • In other words, it is not restricted to a limited number of sites such as replication origins, and this makes the process faster. (
  • But this poses a puzzle: if the alternative process using recombination is more efficient, then why have replication origins at all? (
  • And this process is called replication. (
  • This process represents the inception of an immensely complex and elegant system that is constantly ongoing at tens of thousands of points on the DNA in many cells of the human body, and it all starts with ORCs. (
  • We hope that by mapping this process, others will eventually convert this knowledge into new treatments for DNA replication-related conditions, including many cancers and rare disorders," says Li. (
  • This is why the process is called semiconservative replication . (
  • In a multi-step process, the components of this complex attach (bind) to certain regions of DNA known as origins of replication (or origins), where the process of DNA copying begins. (
  • This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide. (
  • 1) The frist stage is the unravelling of the two orginal strand of DNA, the process is started. (
  • Before a cell divides and DNA is passed from one cell to another, a complex process occurs. (
  • This process is known as replication. (
  • How cells ensure the DNA is accurately replicated during the cell division process. (
  • ture of the mistake, the flanking se- in a process termed metabolic acti- quence, the presence of DNA dam- vation ( Mil er, 1970 ). (
  • However, this process can go wrong, and lead to errors such as the formation of gaps in DNA. (
  • Our studies demonstrate that Cdc6, Cdt1 and Mcm2 play a central role in coordinating growth during the proliferation-differentiation switch in somatic self-renewing systems and that Cdc6 expression is rate-limiting for acquisition of replication competence in primary oocytes. (
  • Geminin deploys multiple mechanisms to regulate Cdt1 before cell division thus ensuring the proper execution of DNA replication. (
  • 1. Is electrophilic or can be metabolical y activated to electrophiles does not alter the linear sequence of nucleotides (or bases) in the DNA, 2. (