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 2.7.7.7.
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 2.7.7.7.
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 2.7.7.7.
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 6.5.1.1 (ATP) and EC 6.5.1.2 (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: www.embo-embl-symposia.org/symposia/2018/EES18-02/index.html 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.
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
PUFs are RNA binding proteins that promote mRNA deadenylation and decay and inhibit translation. Yeast Puf5 is the prototype for studying PUF-dependent gene repression. Puf5 binds to the Pop2 subunit of the Ccr4-Pop2-NOT mRNA deadenylase, recruiting the deadenylase and associated translational repressors to mRNAs. Here we used yeast genetics to show that Puf5 has additional roles in vivo that do not require Pop2. Deletion of PUF5 caused increased sensitivity to DNA replication stress in cells lacking Pop2, as well as in cells mutated for two activities recruited to mRNAs by the Puf5-Pop2 interaction, the deadenylase Ccr4 and the translational repressor Dhh1. A functional Puf5 RNA binding domain was required, and Puf5 cytoplasmic localisation was sufficient for resistance to replication stress, indicating posttranscriptional gene expression control is involved. In contrast to DNA replication stress, in response to the cell wall integrity pathway activator caffeine, PUF5 and POP2 acted in the same genetic
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 ...
Waga, S; Bauer, G; Stillman, B (April 1994). "Reconstitution of complete SV40 DNA replication with purified replication factors ... While at CSHL, Cairns performed important experiments on DNA replication in the bacteria E. coli.[citation needed] James D. ... 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 ...
Tania A. Baker; Kornberg, Arthur (2005). DNA replication. University Science. ISBN 978-1-891389-44-3. Wei, CF; Alianell, GA; ... The DNA fragments cleaved by the same endonuclease can be joined together regardless of the origin of the DNA. Such DNA is ... quadruple-stranded DNA (G-quadruplex) Double-stranded hybrids of DNA and RNA (one strand is DNA, the other strand is RNA) ... The AP endonuclease recognizes this sugar and essentially cuts the DNA at this site and then allows for DNA repair to continue ...
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 function of the genome is directly related to this organizational system, in which there are a ... 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 ...
Poxvirus is unique from other DNA viruses in respect to its locale of replication in the cell. Poxvirus replicates in the ... Moss, Bernard (2013-09-01). "Poxvirus DNA replication". Cold Spring Harbor Perspectives in Biology. 5 (9): a010199. doi:10.1101 ... Poxvirus starts its replication cycle by attaching to host cell receptors. These receptors are thought to be glycosaminoglycan ... "Poxvirus Replication Cycle - Library". www.microbelibrary.org. Archived from the original on 2015-12-20. Retrieved 2015-12-10. ...
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/annurev.bi. ...
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 ...
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 ...
"Supplement to DNA Replication". San Francisco:Freeman. Henikoff, S.; Keene, M. A.; Sloan, S.; Bleskan, J.; Hards, R.; Patterson ...
2002). "DNA Replication Mechanisms". Molecular Biology of the Cell (4th ed.). Garland Science. ISBN 0-8153-3218-1. NBK26850. ... The bases stick out from the pentose-phosphate polymer backbone in DNA and are hydrogen bonded in pairs to their complementary ... DNA) and ribonucleic acid (RNA) are of great importance because they code for the production of all cellular proteins. They are ...
The parent cell replicates its DNA through the process of DNA replication - a process in which DNA undergoes a number of steps ... "What is DNA replication". yourgenome. Balasubramanian, Mohan K.; Bi, Erfei; Glotzer, Michael (2004-09-21). "Comparative ... The parent cell then replicates its DNA and provides the daughter cell with this DNA. The daughter cell is then able to detach ... to formulate a copy of itself during cell division, creating genetically identical DNA to the parent cell-. Once the DNA is ...
DNA replication). 1st g.. *Cinoxacin‡. *Flumequine‡. *Nalidixic acid‡. *Oxolinic acid‡. *Pipemidic acid‡ ...
Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and ... Naphthyridone and quinolone classes of antibiotics prevent bacterial DNA replication by inhibition of DNA unwinding events, and ... Castora, F. J.; Vissering, F. F.; Simpson, M. V. (September 1983). "The effect of bacterial DNA gyrase inhibitors on DNA ... Structure of bacterial DNA gyrase complexed with DNA and two ciprofloxacin molecules (green) ...
"A separate editing exonuclease for DNA replication: the epsilon subunit of Escherichia coli DNA polymerase III holoenzyme". ... Kornberg A, Baker T (2005). DNA Replication (2nd ed.). California: University Science Books. p. 499. ISBN 1-891389-44-0. .. ... It functions as a 3'→5' DNA directed proofreading exonuclease that removes incorrectly incorporated bases during replication.[2 ... a fidelity subunit for DNA replication". Proceedings of the National Academy of Sciences of the United States of America. 80 ( ...
It inhibits nucleic acid synthesis by forming nitroso radicals, which disrupt the DNA of microbial cells.[2][43] This function ... "DNA and Chromosome Mechanics". In Schaechter M, Engleberg NC, DiRita VJ, Dermody T (eds.). Schaechter's Mechanisms of ... DNA replication). 1st g.. *Cinoxacin‡. *Flumequine‡. *Nalidixic acid‡. *Oxolinic acid‡. *Pipemidic acid‡ ...
Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and ... For many gram-negative bacteria DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive ...
It functions by inhibiting DNA gyrase, and a type II topoisomerase, topoisomerase IV,[68][69] necessary to separate bacterial ... Pommier, Yves; Leo, Elisabetta; Zhang, Hongliang; Marchand, Christophe (2010). "DNA Topoisomerases and Their Poisoning by ... "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiology and Molecular Biology Reviews. 61 (3): 377-92. PMC 232616 ... DNA, thereby inhibiting cell division.. Pharmacokinetics[edit]. Ciprofloxacin for systemic administration is available as ...
Maxwell A (February 1999). "DNA gyrase as a drug target". Biochemical Society Transactions. 27 (2): 48-53. doi:10.1042/ ... Maxwell A (August 1993). "The interaction between coumarin drugs and DNA gyrase". Molecular Microbiology. 9 (4): 681-6. doi: ... The potency of novobiocin is considerably higher than that of the fluoroquinolones that also target DNA gyrase, but at a ... Lewis RJ, Tsai FT, Wigley DB (August 1996). "Molecular mechanisms of drug inhibition of DNA gyrase". BioEssays. 18 (8): 661-71 ...
... and adding DNA polymerase to the reaction. This led to exponential DNA replication,[9] greatly amplifying the amounts of DNA ... DNA polymerase. DNA-directed DNA polymerase. I. II. III. IV. V. RNA-directed DNA polymerase. Reverse transcriptase Telomerase. ... However, after each round of replication the mixture needs to be heated above 90 °C to denature the newly formed DNA, allowing ... He was familiar with the use of DNA oligonucleotides as probes for binding to target DNA strands, as well as their use as ...
THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA ... DNA replication). 1st g.. *Cinoxacin‡. *Flumequine‡. *Nalidixic acid‡. *Oxolinic acid‡. *Pipemidic acid‡ ...
... caused over-replication of the DNA and DNA damage leading to cancer cell death. The lab discovered the E2 in the Fanconi Anemia ... Dutta's research has focused on the mammalian cell cycle with an emphasis on DNA replication and repair and on noncoding RNAs. ... His laboratory cloned the cDNAs of many human DNA replication initiation factors and their regulators (Orc3, Orc4, Orc5, Orc6, ... Bell, SP; Dutta, A (2002). "DNA replication in eukaryotic cells". Annual Review of Biochemistry. 71: 333-74. doi:10.1146/ ...
This triggers genomic DNA replication. Usually 100 minutes post-infection Late Phase: Between 140 minutes and 48 hours post- ... Virions contain a core of RNA or DNA within a capsid. A capsid is the protein shell of a virus. Parapoxvirus virions are ... Parapoxviruses belongs to the family of viruses named Poxviridae, family of double-stranded DNA viruses. Parapoxvirus is ... double-stranded DNA genome. The length of the genome ranges from 130 to 150 kilobases. The linear genome is flanked by inverted ...
Early protein "DNA Virus Replication". Daniels R, Sadowicz D, Hebert DN (July 2007). "A very late viral protein triggers the ... A late protein is a viral protein that is formed after replication of the virus. One example is VP4 from simian virus 40 (SV40 ... "The l2 minor capsid protein of low-risk human papillomavirus type 11 interacts with host nuclear import receptors and viral DNA ...
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 ... They also use a typical protein primed DNA polymerase for replication, a property shared with the family Tectiviridae.[citation ... 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 ...
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 ...
... 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?". www.madsci.org. 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 together to make polymers such as DNA and proteins, essential macromolecules of life. Proteins ...
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 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" RK 2 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 ...
... 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 ...
DNA replication occurs during the C period. The D period refers to the stage between the end of DNA replication and the ... "Global effects of DNA replication and DNA replication origin activity on eukaryotic gene expression". Molecular Systems Biology ... These events include the duplication of its DNA (DNA replication) and some of its organelles, and subsequently the partitioning ... G2 phase occurs after DNA replication and is a period of protein synthesis and rapid cell growth to prepare the cell for ...
DNA) in 1953 to more recent advances in genetic engineering. Other key ideas such as the reduction of all life processes to ... in contrast to former narratives in which error replication events (mutations) dominated. Beyond medical ethics and bioethics, ...
... triggering genomic DNA replication by the viral DNA polymerase about 100 minutes post-infection. Replication follows the DNA ... Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral proteins to host ...
This consequently inhibits synthesis of DNA and RNA, and results in antiviral and immunosuppressive effects. It progressed as ... January 2018). "Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens". ...
... where they are involved in the replication of viral DNA. Viral DNA-dependent DNA polymerase synthesizes multiple copies of ... Viral DNA enters the host's nucleus via nuclear pores. Early genes within the viral DNA are transcribed by the host, allowing ... Once the warmer months roll around, viral replication rates dramatically lower to the point of little to no replication, and ... The virus is then assembled in the nucleus, which at this point has been modified such as to become a factory for viral DNA. ...
The primary goal of the Mitochondrial DNA Replication Group is to understand the role of the replication apparatus in the ... This schematic diagram of the Mitochondrial DNA Replication Group intermediate shows the critical proteins required for DNA ... Human DNA Polymerase Gamma Mutation Database. To see the complete list, visit the Human DNA Polymerase Gamma Mutation Database ... Innovative technologies shed light on mitochondrial DNA replication *Exploring the biological effects of mitochondrial peptides ...
... the DNA Replication Fidelity Group performs research aimed at understanding the DNA transactions that determine DNA replication ... When DNA damage is not repaired prior to replication, certain lesions can impede replication fork progression and reduce ... Replication infidelity and its role in disease and aging. *Structure-function studies of replication proteins, especially DNA ... The genetics and biochemistry of eukaryotic DNA mismatch repair. Thomas A. Kunkel, Ph.D., leads the DNA Replication Fidelity ...
Kelly, T.J., Jr., 1982, Organization and replication of adenovirus DNA, in: Organization and Replication of Viral DNA (A.S. ... Schilling, R., Weingartner, B., and Winnacker, E.-L., 1975, Adenovirus type 2 DNA replication. II. Termini of DNA replication, ... Adenovirus DNA replication: Isolation of a soluble replication system and analysis of the in vitro DNA product, J. Biol. Chem. ... Specific binding of a cellular DNA replication protein to the origin of replication of adenovirus DNA, Proc. Natl. Acad. Sci. U ...
The research concluded that the altered DNA replication mechanism of the high-risk viruses makes them lethal. Specific DNA ... DNA replication in HPV. Article by Dante LaPenta Photo by Kathy F. Atkinson May 22, 2018 ... The UD researchers have worked on DNA replication in bacteria and human cells for a long time, but a discussion with Joseph ... Esther Biswas-Fiss (right) and Subhasis Biswas are investigating genetic variations in the DNA replication origins of HPV and ...
Most of the topics in this book revolve around deoxyribonucleic acid (DNA), although some of... ... A review of evidence for a DNA replication factory through which DNA moves.)PubMedCrossRefGoogle Scholar ... Birge E.A. (2000) Replication and Analysis of DNA. In: Bacterial and Bacteriophage Genetics. Springer, New York, NY. * DOI ... Kornberg, A., Baker, T.A. (1992). DNA Replication, second edition. San Francisco: W.H. Freeman.Google Scholar ...
... is the process of unraveling the Double Helix to create a template of matching DNA strands which creates a second set of DNA ... Learn about the DNA replication steps to better understand the process..... DNA Replication Errors DNA replication errors that ... More About Dna Replication. What is DNA Replication? The answer is essential to understanding the basic rules of genetics. An ... DNA replication is an important process resulting in the production of another copy of the DNA strand. Learn about the DNA ...
But some replication errors make it past these mechanisms, thus becoming permanent mutations. Moreover, when the genes for the ... The majority of these mistakes are corrected through DNA repair processes. Repair enzymes recognize structural imperfections ... DNA repair enzymes themselves become mutated, mistakes begin accumulating at a much higher rate. In eukaryotes, such mutations ... Although DNA usually replicates with fairly high fidelity, mistakes do happen. ...
... teins Involved in DNA Replication which was held September 19 to 23,1983 at Vitznau, near Lucerne, in Switzerland. The aim of ... different DNA poly- merases, DNA primases, DNA dependent ATPases, helicases, DNA liga- ses, DNA topoisomerases, exo- and ... Initiation of DNA Synthesis on Single-Stranded DNA Templates in Vitro Promoted by the Bacteriophage λ O and P Replication ... Proteins Involved in DNA Replication. Editors. * Ulrich Huebscher Series Title. Advances in Experimental Medicine and Biology. ...
... of DNA Replication Semi-conservative Mode of Replication/Meselson and Stahl Experiment Enzymes of Replication Prokaryotic DNA ... 3 DNA Replication CONCEPT OUTLINE Introduction Chemistry of DNA Synthesis Modes ...
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 ... organization of duplicated DNA. During DNA replication, all the information in the mother cell must be transmitted to the ...
Lethal DNA re-replication may be used to attack cancer cells DNA over-replication is a phenomenon that can have devastating ... 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 ...
GO:0006270 DNA replication initiation Molecular Function. GO:0005524 ATP binding GO:0003677 DNA binding GO:0003678 DNA helicase ... DNA replication licensing factor MCM7, IPR008050. In addition to its role in initiation of DNA replication, Mcm2 is able to ... A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication.. Proc. Natl. Acad. ... Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.. Cell 139 719-30 2009 ...
1989) Highly efficient DNA synthesis by the phage phi29 DNA polymerase. Symmetrical mode of DNA replication. J Biol Chem 264: ... Active DNA unwinding dynamics during processive DNA replication. José A. Morin, Francisco J. Cao, José M. Lázaro, J. Ricardo ... In many DNA replication systems, replication and unwinding of the fork are carried out by the coordinate action of different ... Duplication of double-stranded DNA (dsDNA) requires a fine-tuned coordination between the DNA replication and unwinding ...
... it has been unclear whether the replication regulatory protein is also involved in the replication stress response. We have ... identified the fundamental mechanism of replication stress control, which is a major cause of cancer. Hopefully our work will ... IBS scientists revealed that ATAD5 actively deals with replication stress, in addition to its known function to prevent such ... How cells relieve DNA replication stress ATAD5 raised its profile as an active tumor suppressor by promoting DNA replication ...
Break-induced replication (BIR) refers to recombination-dependent DNA synthesis initiated from one end of a DNA double-strand ... 2010) Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly. Genes ... 1996) Double-strand break repair in the absence of RAD51 in yeast: A possible role for break-induced DNA replication. Proc Natl ... Break-induced replication occurs by conservative DNA synthesis. Roberto A. Donnianni and Lorraine S. Symington ...
Without replication, each cell lacks enough genetic material... ... DNA replication is important because it creates a second copy ... of DNA that must go into one of the two daughter cells when a cell divides. ... What Is DNA Replication?. A: DNA replication is a process in which DNA is duplicated so that it can be integrated into a new ... How Does DNA Replicate?. A: DNA replication is a process whereby a single DNA molecule produces two identical copies. Each side ...
Previous section The Chemistry of the Addition of Substrates of DNA Replication Next section DNA Proof-Reading and Repair ... While DNA replication does occur in the 5 to 3 direction, the reason is not because 3 to 5 replication is chemically ... DNA replication occurs in the 5 to 3 direction because 3 to 5 replication is chemically impossible. Explain your answer. ... Lagging strand synthesis is more complex because of the requirement for DNA replication to take place in the 5 to 3 direction ...
... two strands of DNA separate, and each separate strand forms a template to make a new strand. The replication process results in ... What enzymes are involved in DNA replication?. A: Many enzymes are involved in DNA replication, including DNA helicase, DNA ... What is DNA polymerase 1?. A: DNA polymerase I is an enzyme that plays a role in the process of DNA replication, according to ... What best describes the difference between transcription and DNA replication?. * How does an unwound strand of DNA begin to ...
When RNA-DNA hybrids persist, cells experience an increase in mutation rate and problems with DNA replication. Okazaki fragment ... Replicative DNA helicases are essential cellular enzymes that unwind duplex DNA in front of the replication fork during ... Does the Semiconservative Nature of DNA Replication Facilitate Coherent Phenotypic Diversity? It has been clear for over sixty ... Escherichia coli PriA and PriC recruit the replication machinery to a collapsed replication fork after it is repaired and needs ...
DNA) replication is an evolutionarily semi‐conserved process that involves a mechanism to unwind the parent DNA strand, the ... Keywords: DNA replication; mammalian cells; replication factories; initiation; replication fork; termination; replication fork ... Donley N and Thayer MJ (2013) DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing ... 1) DNA damage (red "D") in the leading or lagging strand stalls DNA polymerase. As DNA helicases continue to unwind DNA, RPA. ...
DNA replication in order to explore semi-conservative replication and identify specific enzymes and their roles in replication. ... Using three simulations, students will interact with DNA replication to explore semi-conservative replication and identify ... Explore how the structure of DNA supports its semi-conservative replication. *Identify the name and function of several key ... Learn the basic functions of the following DNA replication enzymes: helicase, primase, ligase, polymerase I and III. ...
Non-transcriptional control of DNA replication by c-Myc.. Dominguez-Sola D1, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, ... Here we show that c-Myc has a direct role in the control of DNA replication. c-Myc interacts with the pre-replicative complex ... These findings identify a critical function of c-Myc in DNA replication and suggest a novel mechanism for its normal and ... Overexpression of c-Myc causes increased replication origin activity with subsequent DNA damage and checkpoint activation. ...
Moreover, because errors arising during DNA replication and gene amplification result in chromosomal abnormalities often found ... Leveraging a novel system designed to examine the double-strand DNA breaks that occur as a consequence of gene amplification ... during DNA replication, Whitehead Institute scientists are bringing new clarity to the causes of such genomic damage. ... "Replication fork progression during re-replication requires the DNA damage checkpoint and double-strand break repair" ...
This book reviews the latest trends and future directions of DNA replication research emphasizing the latest results on ... as well as the timing of DNA replications, mechanisms of initiation, DNA chain elongation and termination of DNA replication, ... Reviews comprehensive compilation of the newest information on DNA replication *Approaches issues related to DNA replication ... cell cycle-dependent regulation of DNA replication, the nature of replication stress and cells strategy to deal with the ...
DNA polymerases carry out a large variety of synthetic transactions during DNA replication, DNA recombination and DNA repair. ... Eukaryotic DNA polymerases in DNA replication and DNA repair.. Burgers PM1. ... The function of DNA polymerase epsilon in DNA replication may be restricted to that of Okazaki fragment maturation. In contrast ... DNA polymerase alpha is almost exclusively required for the initiation of DNA replication and the priming of Okazaki fragments ...
1994 The 3′→5′ exonucleases of both DNA polymerases δ and ε participate in correcting errors of DNA replication in ... DNA Replication Error-Induced Extinction of Diploid Yeast. Alan J. Herr, Scott R. Kennedy, Gary M. Knowels, Eric M. Schultz and ... DNA Replication Error-Induced Extinction of Diploid Yeast. Alan J. Herr, Scott R. Kennedy, Gary M. Knowels, Eric M. Schultz and ... DNA Replication Error-Induced Extinction of Diploid Yeast. Alan J. Herr, Scott R. Kennedy, Gary M. Knowels, Eric M. Schultz and ...
Adenovirus DNA Replication. Rob C. Hoeben and Taco G. Uil. Herpes Simplex Virus DNA Replication. Sandra K. Weller and Donald M ... Epstein-Barr Virus DNA Replication. Wolfgang Hammerschmidt and Bill Sugden. Poxvirus DNA Replication. Bernard Moss. Appendix. ... Regulating DNA Replication in Eukarya. Khalid Siddiqui, Kin Fan On, and John F.X. Diffley. Regulating DNA Replication in Plants ... Archaeology of Eukaryotic DNA Replication. Kira S. Makarova and Eugene V. Koonin. Human Mitochondrial DNA Replication. Ian J. ...
... simple manipulative set for studying DNA, including structure, replication, and transcription. This wonderfully flexible model ... DNA, Replication and Transcription Set. Item # 211119 *bvseo_sdk, java_sdk, bvseo-4.0.0 ... DNA Gel Electrophoresis. Carolina makes DNA gel electrophoresis easy when studying forensics or genetics. Theres a simple set ... DNA Learning Center. DNA Learning Center resources are the best in scientific educational materials. Kits and materials for ...
Eukaryotic DNA replication is discussed in this video with Colsd Spring Harbors Bruce Stillman, who takes us through the ... which focussed on eukaryotic DNA replication. Bruce also tells us about the techniques he uses in his research, the challenges ...
Now, in work done mainly in yeast, researchers are finding that this exquisite control of DNA replication is achieved by a ... but early results suggest that these species use similar proteins for controlling DNA replication. ... As the cells of higher organisms prepare to divide, they face a tremendous logistic problem: How to copy all of their DNA once- ... complex of proteins interacting with specific short DNA sequences. Theyve also identified several of the proteins that form ...

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