• The major enzymatic functions carried out at the replication fork are well conserved from prokaryotes to eukaryotes, but the replication machinery in eukaryotic DNA replication is a much larger complex, coordinating many proteins at the site of replication, forming the replisome. (wikipedia.org)
  • Multiple replicative proteins assemble on and dissociate from these replicative origins to initiate DNA replication. (wikipedia.org)
  • Association of the origin recognition complex (ORC) with a replication origin recruits the cell division cycle 6 protein (Cdc6) to form a platform for the loading of the minichromosome maintenance (Mcm 2-7) complex proteins, facilitated by the chromatin licensing and DNA replication factor 1 protein (Cdt1). (wikipedia.org)
  • The pre-RC formation involves the ordered assembly of many replication factors including the origin recognition complex (ORC), Cdc6 protein, Cdt1 protein, and minichromosome maintenance proteins (Mcm2-7). (wikipedia.org)
  • Michael Hendzel (right) co-led a study that revealed the gel-like nature of chromatin, the complex package of DNA and proteins contained within the nucleus of our cells. (ualberta.ca)
  • University of Alberta researchers have found an answer to a fundamental question in genomic biology that has eluded scientists since the discovery of DNA: Within the nucleus of our cells, is the complex package of DNA and proteins called chromatin a solid or a liquid? (ualberta.ca)
  • Right now, all of our understanding of gene regulation is largely based on the assumption of freely moving proteins that find DNA and whose accessibility is only regulated by the blocking of that movement. (ualberta.ca)
  • All of our chromosomes are made from chromatin, which is half histone (or structural) proteins and half DNA, organized into long strings with bead-like structures (nucleosomes) on them. (ualberta.ca)
  • Through a combination of biochemical analysis, using purified proteins and cell-free extracts of Xenopus laevis eggs, and in vivo cell biological analysis using established human cell lines, my group is identifying key targets of ubiquitin and SUMO modification in the DNA damage response. (lancaster.ac.uk)
  • DNA replication origins retain mobile licensing proteins. (yeastgenome.org)
  • Bailis JM and Forsburg SL (2004) MCM proteins: DNA damage, mutagenesis and repair. (yeastgenome.org)
  • Histone H3 is one of the DNA-binding proteins found in the chromatin of all eukaryotic cells. (fishersci.com)
  • H3 along with four core histone proteins binds to DNA forming the structure of the nucleosome. (fishersci.com)
  • We find that this type of non-canonical fork convergence in fission yeast is prone to trigger deletions between repetitive DNA sequences via a mechanism we call Inter-Fork Strand Annealing (IFSA) that depends on the recombination proteins Rad52, Exo1 and Mus81, and is countered by the FANCM-related DNA helicase Fml1. (elifesciences.org)
  • Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)
  • Histones are basic nuclear proteins responsible for nucleosome structure of the chromosomal fiber in eukaryotes. (nih.gov)
  • In mammals, this process relies on the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) that generates crossover recombination events (COs) [ 1 ]. (nature.com)
  • Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase-Pol ε Interaction. (yeastgenome.org)
  • Collapsed forks can be rescued by homologous recombination, which restarts replication. (elifesciences.org)
  • This so-called recombination-dependent replication (RDR) helps ensure that DNA is fully replicated prior to sister chromatid segregation, thereby avoiding mitotic catastrophes. (elifesciences.org)
  • T opoisomerase enzymes I and II play a critical role in preserving DNA topology by producing transient single- and double-strand DNA breaks that relieve supercoiling during replication, recombination, chromosomal decondensation, and RNA transcription. (cancernetwork.com)
  • Homologous recombination (HR) is an essential mechanism for the repair of DNA double-strand breaks and damaged replication forks and is associated with genetic disorders, cancer and aging. (muni.cz)
  • Mechanisms for maintaining genetic information during cell division and the generation of genetic variation: replication, mitosis, meiosis, recombination. (lu.se)
  • Eukaryotic origins of replication control the formation of several protein complexes that lead to the assembly of two bidirectional DNA replication forks. (wikipedia.org)
  • Bacterial origins regulate orisome assembly, a nuclei-protein complex assembled on the origin responsible for unwinding the origin and loading all the replication machinery. (wikipedia.org)
  • In E. coli, the direction for orisome assembly are built into a short stretch of nucleotide sequence called as origin of replication (oriC) which contains multiple binding sites for the initiator protein DnaA (a highly homologous protein amongst bacterial kingdom). (wikipedia.org)
  • Landmark discovery of the physical state of complex DNA and protein "packages"-called chromatin-in a cell's nucleus could lead to better understanding of diseases such as cancer. (ualberta.ca)
  • The ORC-Cdc6 complex (product 1) assembles in step 1 around origin DNA and with the help of another replication initiator protein, Cdt1, it recruits the Mcm2-7 hexamer to the origin in step 2. (nature.com)
  • Changing protein-DNA interactions promote ORC binding-site exchange during replication origin licensing. (yeastgenome.org)
  • Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex. (yeastgenome.org)
  • Structural changes in Mcm5 protein bypass Cdc7-Dbf4 function and reduce replication origin efficiency in Saccharomyces cerevisiae. (yeastgenome.org)
  • Activation of the MCM complex at origins by cyclin-dependent kinases and the CDC7 protein kinase (P06243) leads to initiation of DNA synthesis. (yeastgenome.org)
  • and, regulation of biological processes such as chromosomal folding, protein secretion and intracellular signaling. (berkeley.edu)
  • The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)
  • Biochemical processes as diverse as the elastic response of DNA, protein-induced DNA bending, chromosomal segregation, replication, transcription, translation, protein translocation across membranes, catalyzed protein and nucleic acid folding and unfolding, and even the ubiquitous processes of induced-fit molecular recognition, are all examples in which forces and torques develop in molecules as they move along their reaction coordinates. (berkeley.edu)
  • We are studying the structural basis of protein-DNA interactions and their relevance in the processes of control of gene expression using single molecule manipulation methods. (berkeley.edu)
  • In prokaryotes, and specially in eukaryotes, replication and transcription regulation involve the interaction of many specialized protein factors at regulator locations on the sequence to ensure correct sequence recognition, initiation, processivity, fidelity, and kinetic control. (berkeley.edu)
  • Expression of the L1 protein using recombinant DNA technology produces noninfectious virus-like particles (VLPs). (cdc.gov)
  • Bioinformatic analyses of DNA- and protein sequences. (lu.se)
  • The RECQL4 protein, deficient in Rothmund-Thomson syndrome is active on telomeric D-loops containing DNA metabolism blocking lesions. (medscape.com)
  • By means of DNA sequencing of a large sample collection of the pathogen from across the United States, we studied the gene for the bacterium's highly diverse OspC protein, protective immunity against which develops in animals. (cdc.gov)
  • In mammals, functional analysis of the individual RAD51 paralogues in cell lines has shown similar but non-redundant contributions in DNA repair processes such as HR efficiency, RAD51 nuclear focus formation, sensitization to mitomycin C (MMC) and protection of perturbed replications forks [ 11 ]. (nature.com)
  • Eukaryotic DNA replication initiates at multiple origin sites along each chromosome and terminates when replication forks (RFs) from adjacent origins converge. (elifesciences.org)
  • Completion of genome duplication is challenged by structural and topological barriers that impede progression of replication forks. (ku.dk)
  • This is demonstrated by the formation of DNA double strand breaks (DSBs), considered to be the most toxic DNA lesions, at stalled replication forks. (avhandlingar.se)
  • Initiation of eukaryotic DNA replication is the first stage of DNA synthesis where the DNA double helix is unwound and an initial priming event by DNA polymerase α occurs on the leading strand. (wikipedia.org)
  • with the formation of the pre-replication complex (pre-RC) being a key intermediate in the replication initiation process. (wikipedia.org)
  • Once the pre-RC is formed, activation of the complex is triggered by two kinases, cyclin-dependent kinase 2 (CDK) and Dbf4-dependent kinase (DDK) that help transition the pre-RC to the initiation complex before the initiation of DNA replication. (wikipedia.org)
  • For the same reason, the initiation of DNA replication is highly regulated. (wikipedia.org)
  • Chromosome replication in bacteria is regulated at the initiation stage. (wikipedia.org)
  • DDK regulates replication initiation by controlling the multiplicity of Cdc45-GINS binding to Mcm2-7. (yeastgenome.org)
  • Bryant JA and Aves SJ (2011) Initiation of DNA replication: functional and evolutionary aspects. (yeastgenome.org)
  • Essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells, associates with the origins of DNA replication to form part of the pre-replicative complex. (yeastgenome.org)
  • In this chapter, we mainly discuss the coordination regulations between DNA replication initiation and other cell cycle events that ensure genomic integrity. (intechopen.com)
  • DNA replication occurs once and only once per cell cycle mainly regulated by DNA replication initiation factors in eukaryotic cells. (intechopen.com)
  • The pre-replication complex (pre-RC) assembly or the DNA replication licensing is the first step in DNA replication initiation, characterized by the sequential recruitment of ORCs, Cdc6, Cdt1 and MCMs to the DNA replication origins to form the pre-RC at the end of mitosis ( Bell and Dutta 2002 ). (intechopen.com)
  • Here, we show that mild replication stress increases the frequency of chromosomal lesions that are transmitted to daughter cells. (ku.dk)
  • Ionizing radiation induces a range of different DNA lesions. (avhandlingar.se)
  • In terms of mutation frequency and mammalian cell survival, the most critical of these lesions is the DNA double-strand break (DSB). (avhandlingar.se)
  • The predominant form of this condition is caused by a recessive mutation in one of the essential components of the nucleotide excision repair (NER) system, whose main function is to snip out molecular DNA lesions caused by exposure of skin epithelium to ultraviolet light. (the-scientist.com)
  • Access to DNA is a prerequisite to the execution of essential cellular processes that include transcription, replication, chromosomal segregation, and DNA repair. (rockefeller.edu)
  • In eukaryotes, the vast majority of DNA synthesis occurs during S phase of the cell cycle, and the entire genome must be unwound and duplicated to form two daughter copies. (wikipedia.org)
  • This mechanism is conserved from prokaryotes to eukaryotes and is known as semiconservative DNA replication. (wikipedia.org)
  • The DNA glycosylase MutYH is highly conserved throughout evolution, and homologs are found in most eukaryotes and prokaryotes examined. (avhandlingar.se)
  • Priming of the DNA helix consists of the synthesis of an RNA primer to allow DNA synthesis by DNA polymerase α. (wikipedia.org)
  • This hydrolysis drives DNA synthesis to completion. (wikipedia.org)
  • MCM2-7 complexes unwind the double stranded DNA at the origins, recruit DNA polymerases and initiate DNA synthesis. (yeastgenome.org)
  • Regardless of its precise form, collapse renders the fork incompetent for further DNA synthesis. (elifesciences.org)
  • The S phase is marked by synthesis of DNA. (differencebetween.net)
  • To achieve this, cells need a balanced supply of deoxyribonucleoside triphosphates (dNTPs), the precursors for DNA synthesis. (avhandlingar.se)
  • Tumor risk can also be influenced by mutations in genes that control the fidelity of DNA replication, the efficacy of DNA repair, and the checkpoint controls involved in DNA synthesis and chromosomal mechanics. (the-scientist.com)
  • 3] This antagonism might be related to topoisomerase I inhibition of DNA synthesis, which is required for the cytotoxic effect of topoisomerase II-induced cleavable complexes. (cancernetwork.com)
  • The replisome is responsible for copying the entirety of genomic DNA in each proliferative cell. (wikipedia.org)
  • Problems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. (elifesciences.org)
  • Faithful DNA replication is essential and the induction of replication stress may have profound effects on genomic integrity. (avhandlingar.se)
  • Mice with mutations in genes that regulate an important DNA replication complex, called the minichromosome maintenance complex or MCM, are susceptible to genomic instability and cancer. (nih.gov)
  • 168" /mol_type="genomic DNA" /strain="168" /db_xref="taxon:224308" gene 4866. (biojava.org)
  • Opposite to the mitotic spindle, the separation of chromosomal replication is done through the cell membrane. (differencebetween.net)
  • Together, these data indicate that restoration of DNA or chromatin integrity at loci prone to replication problems requires mitotic transmission to the next cell generations. (ku.dk)
  • The DnaC helicase loader then interacts with the DnaA bound to the single-stranded DNA to recruit the DnaB helicase, which will continue to unwind the DNA as the DnaG primase lays down an RNA primer and DNA Polymerase III holoenzyme begins elongation. (wikipedia.org)
  • We show that the number of such 53BP1 nuclear bodies increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. (ku.dk)
  • Rothmund-Thomson syndrome (poikiloderma congenitale) has been attributed to mutations of the RECQL4 gene on 8q24, which encodes a RecQ DNA helicase. (medscape.com)
  • Exhibits a Magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. (lu.se)
  • Miller CLW and Winston F (2023) The conserved histone chaperone Spt6 is strongly required for DNA replication and genome stability. (yeastgenome.org)
  • DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (joplink.net)
  • The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. (nih.gov)
  • This gene is intronless and encodes a replication-dependent histone that is a member of the histone H1 family. (nih.gov)
  • Future work in the lab will focus on identifying genes that induce DNA damage in response to short telomeres, identifying how telomeres are processed and how telomere elongation is regulated. (hopkinsmedicine.org)
  • To synthesize DNA, the double-stranded DNA is unwound by DNA helicases ahead of polymerases, forming a replication fork containing two single-stranded templates. (wikipedia.org)
  • Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution. (nih.gov)
  • Generally, problems with DNA replication or repair during periods of rapid cell division can cause instability in the genome, which results in cellular stress and inflammation. (nih.gov)
  • Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma. (medscape.com)
  • Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. (hopkinsmedicine.org)
  • Collectively, we propose that fission yeast Stn1 primarily safeguards the semi-conservative DNA replication at telomeres and subtelomeres. (nih.gov)
  • My research interests are in understanding how cells normally function to prevent, or reverse, deleterious genetic alterations and chromosomal abnormalities. (lancaster.ac.uk)
  • A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis. (yeastgenome.org)
  • When we probed neutral-neutral 2D gels for subtelomere regions, we found no Y-arc-shaped replication intermediates in cycling cells. (nih.gov)
  • Although this can seriously undermine genome integrity, the fate of DNA with unresolved replication intermediates is not known. (ku.dk)
  • Cells possess a complex network of DNA damage response (DDR) pathways that can detect problems with genome integrity and initiate a series of responses, such as DNA repair, arrest of cell cycle progression until the problem is rectified or, if the problem is too great, programmed cell death. (lancaster.ac.uk)
  • DNA sequences containing these sites were initially isolated in the late 1970s on the basis of their ability to support replication of plasmids, hence the designation of autonomously replicating sequences (ARS). (wikipedia.org)
  • The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. (nature.com)
  • The microarray technology is based on the hybridization of labelled DNA or RNA molecules to complementary sequences that are immobilized on a solid substrate. (tutorialspoint.com)
  • Principle of DNA MicroarrayThe principle of DNA microarray technology is based on the hybridization of complementary sequences of nucleic acid molecules. (tutorialspoint.com)
  • Repair of mitomycin-C-induced chromosomal aberrations was impaired in RAD51B/Rad51b-c.92delT human and mouse somatic cells in vitro and in explanted mouse bone marrow cells. (nature.com)
  • DSB left unrepaired or mis-repaired may result in chromosomal aberrations that can lead to permanent genetic changes or cell death. (avhandlingar.se)
  • Replication is bi-directional and originates at a single origin of replication (OriC). (wikipedia.org)
  • There are 11 DnaA binding sites/boxes on the E. coli origin of replication out of which three boxes R1, R2 and R4 (which have a highly conserved 9 bp consensus sequence 5' - TTATC/ACACA ) are high affinity DnaA boxes. (wikipedia.org)
  • Replication starts at origins of replication. (wikipedia.org)
  • These events are initiated by the formation of the pre-replication complex (pre-RC) at the origins of replication. (wikipedia.org)
  • Introduction DNA microarrays are powerful tools for analysing gene expression patterns, detecting DNA mutations, and identifying genetic variations. (tutorialspoint.com)
  • Introduction Bacterial Artificial Chromosome (BAC) is a powerful tool in Genetic Research Bacterial Artificial Chromosome (BAC) is a widely used tool in genetic research for the manipulation and study of DNA. (tutorialspoint.com)
  • HR repairs DNA damage by copying the correct genetic information from an intact chromosomal template, which is critically dependent on the recombinase RAD51. (muni.cz)
  • The priming event on the lagging strand establishes a replication fork. (wikipedia.org)
  • Ataxia telangiectasia mutated (ATM) is a DNA damage kinase which is activated by double-strand DNA breaks. (bvsalud.org)
  • RESULTS: ATM inhibition increased double-strand DNA breaks at replication foci in HNC cell lines. (bvsalud.org)
  • They can carry large inserts of DNA up to 300 kilobases in size, making them ideal for studying the function and organization of genes and genomes. (tutorialspoint.com)
  • The importance of apoptosis is exemplified by the vertebrate adaptive immune system, in which B lymphocytes, as they differentiate from their precursor cells, rearrange the DNA of immunoglobulin genes to generate a vast number of potential antibodies. (the-scientist.com)
  • Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination. (elifesciences.org)
  • However, replication restart is relatively slow and, therefore, replication termination may frequently occur by an active fork converging on a collapsed fork. (elifesciences.org)
  • Here we report the cryo-EM structure at 3.3 Å resolution of the yeast ORC-Cdc6 bound to an 85-bp ARS1 origin DNA. (nature.com)
  • The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. (nature.com)
  • Accordingly, Rad51b-c.92delT variant reduced replication fork progression of patient-derived lymphoblastoid cell lines and pluripotent reprogramming efficiency of primary mouse embryonic fibroblasts. (nature.com)
  • The process of semiconservative replication for the site of DNA replication is a fork-like DNA structure, the replication fork, where the DNA helix is open, or unwound, exposing unpaired DNA nucleotides for recognition and base pairing for the incorporation of free nucleotides into double-stranded DNA. (wikipedia.org)
  • 2022. Probing the mechanisms of two exonuclease domain mutators of DNA polymerase ε. (nih.gov)
  • 2022. Ribonucleotide incorporation by eukaryotic B-family DNA replicases and its consequences. (nih.gov)
  • Meiosis is a sexual division that halves the diploid somatic chromosomal complement to a haploid state. (nature.com)
  • This transition involves the ordered assembly of additional replication factors to unwind the DNA and accumulate the multiple eukaryotic DNA polymerases around the unwound DNA. (wikipedia.org)
  • Rad51b c.92delT/c.92delT mice exhibited meiotic DNA repair defects due to RAD51 and HSF2BP/BMRE1 accumulation in the chromosome axes leading to a reduction in the number of crossovers. (nature.com)
  • MutYH functions as a base excision repair DNA glycosylase that excises adenines misincorporated opposite 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), one of the most stable products of oxidative DNA damage. (avhandlingar.se)
  • A prerequisite for a multicellular organism to survive is the ability to correctly replicate and repair DNA while minimizing the number of heritable mutations. (avhandlingar.se)
  • Problems with DNA replication and repair may also contribute to developmental defects and possibly to pregnancy loss, but the reasons for these problems are not well understood. (nih.gov)
  • Researchers led by John Schimenti, Ph.D., at Cornell University studied mice to help determine how problems with DNA replication and repair affect embryonic development. (nih.gov)
  • The researchers also noted that the skewed gender ratios likely were not linked to all types of DNA replication and repair problems, but they may be limited to those that cause certain types of chromosomal damage. (nih.gov)
  • Xeroderma pigmentosum, for example, stems from a specific DNA repair deficiency. (the-scientist.com)
  • Poly(ADP-ribose) polymerases (PARP) act as DNA damage sensors that produce poly(ADP-ribose) (PAR) chains at double-strand breaks, facilitating the recruitment of repair factors. (bvsalud.org)
  • DNA adducts are subject to DNA repair and necrosis of the cell, which will alter the cumulative dose estimate depending if the exposure is intermittent (allowing for DNA repair time) or constant (no DNA repair time). (who.int)
  • availability of large amounts (erythrocytes in whole blood), availability of methods for chemical identification (specific and sensitive), and the well-defined life span due to absence of DNA repair (Ogawa et al. (who.int)
  • Participates in DNA replication and may participate in repair. (lu.se)
  • RDR can initiate from a collapsed fork where the DNA is either broken or remains intact. (elifesciences.org)
  • Introduction DNA supercoiling is the twisting or coiling of the double helix structure of DNA, resulting in a strain on the molecule. (tutorialspoint.com)
  • Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase. (hopkinsmedicine.org)
  • We conclude that the loss of telomere and subtelomere DNAs in stn1-1 cells at the restrictive temperature is caused by very frequent replication fork collapses specifically in subtelomere regions. (nih.gov)
  • TYPES OF REPLICATION 6 Hypothetically, therecouldbethreepossible waysthat DNAreplication occur: Conservative replication: Bothparental strands stay together afterDNAreplication. (slideshare.net)
  • Additional mechanisms that may control DNA accessibility in vivo include chromatin compaction and phase separation - processes that are beginning to be understood. (rockefeller.edu)
  • The anti-inflammatory properties of testosterone appear to protect male mouse embryos from certain types of DNA damage and inflammation that are fatal to female mouse embryos, according to a recent NIH-supported study. (nih.gov)
  • Treating pregnant mice with testosterone or ibuprofen improved the survival of female embryos with DNA damage and resulted in normal gender ratios among the mouse pups. (nih.gov)
  • Our work shows how DNA damage and inflammation compromise the health of female mouse embryos," said Cornell's Dr. Schimenti. (nih.gov)
  • Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. (nih.gov)
  • In this article, we will discuss the principle, types, and steps involved in the DNA microarray technology. (tutorialspoint.com)
  • In this thesis methods of computational chemistry have been used to examine DNA damaging processes initiated by ionizing radiation, free radicals, or Low-Energy Electrons (LEE). (avhandlingar.se)