• DDX5 is required for cell proliferation by controlling the transcription of genes expressing DNA replication proteins in cancer cells in which the DDX5 locus is amplified, and this has uncovered a dependence on DDX5 for cell proliferation. (aacrjournals.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)
  • 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)
  • We performed MS label-free quantification to determine which proteins are enriched in an active replication fork in T. brucei (Chapter 3). (umass.edu)
  • We identified 410 proteins, including key DNA replication factors and proteins associated with transcription, chromatin organization, DNA repair and mRNA splicing. (umass.edu)
  • Around 25% of the proteins identified were of unknown function that might have the potential to be essential trypanosome-specific replication proteins. (umass.edu)
  • For cohesion assays, demembranated sperm nuclei are incubated in interphase extract, where they undergo rapid and synchronous DNA replication and cohesion establishment through the recruitment of proteins and other factors (e.g., nucleotides) from the extract. (nih.gov)
  • 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)
  • Similar but distinct recruitment of certain DNA damage response proteins also occurs during infection. (mdpi.com)
  • Finally, we demonstrate that Polycomb proteins and associated epigenetic marks are crucial for the control of the replication timing of the INK4a/ARF locus during senescence. (plos.org)
  • This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. (rupress.org)
  • Differentially expressed candidate genes for ageing previously identified in the human blood transcriptome up-regulated in PP cows were mainly associated with T-cell function ( CCR7 , CD27 , IL7R , CAMK4 , CD28 ), mitochondrial ribosomal proteins ( MRPS27 , MRPS9 , MRPS31 ), and DNA replication and repair ( WRN ). (biomedcentral.com)
  • To investigate the dynamic changes in chromatin organization at and surrounding replication origins, we used micrococcal nuclease (MNase) to generate genome-wide chromatin occupancy profiles of nucleosomes, transcription factors, and replication proteins through consecutive cell cycles in Saccharomyces cerevisiae. (duke.edu)
  • The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. (nih.gov)
  • We have reconstituted chromatin replication with purified proteins, which is providing unprecedented insights into chromosome biology. (crick.ac.uk)
  • We have reconstituted the process of chromatin replication with purified proteins. (crick.ac.uk)
  • Histones are evolutionarily conserved DNA-binding proteins. (aging-us.com)
  • Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion. (idrblab.net)
  • Her interests are directed towards understanding the fidelity of human DNA polymerases in addition to studying proteins involved in mismatch repair processes. (nih.gov)
  • In the study now published in Cell Reports , the research team led by Prof. Wolfram Brune (HPI) and Prof. Jens B. Bosse (MHH, CSSB, HPI) used live-cell imaging and photo-oligomerization methods to show that the HCMV proteins UL112-113 undergo liquid-liquid phase separation, which supports the formation of replication compartments in the nucleus. (leibniz-interact.de)
  • In this context, the UL112-113 proteins perform an essential function by creating a replication-promoting environment around viral genomes," explains Prof. Wolfram Brune, head of the HPI research department Virus-Host-Interaction . (leibniz-interact.de)
  • Phase separation by the UL112-113 proteins is not only important for the spatial organization of HCMV pre-replication compartments, but also essential for the recruitment of proteins for viral DNA replication," Prof. Jens B. Bosse, head of the HPI-associated Quantitative Virology group, comments on the results. (leibniz-interact.de)
  • Differential requirement of Srs2 helicase and Rad51 displacement activities in replication of hairpin-forming CAG/CTG repeats. (tufts.edu)
  • The Srs2 helicase unwinds DNA hairpins, facilitates replication, and prevents repeat instability and fragility. (tufts.edu)
  • Here, using SRS2 separation-of-function alleles, we show that in the absence of Srs2 recruitment to PCNA or in helicase-deficient mutants, breakage at a CAG/CTG repeat increases. (tufts.edu)
  • intact Mcm10 coiled-coil interaction surface is important for origin melting, helicase assembly and the recruitment of Pol-α to Mcm2-7. (fsu.edu)
  • The replication fork helicase is composed of Cdc45, Mcm2-7 and GINS (CMG). (fsu.edu)
  • Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. (nih.gov)
  • In summary, our work provides fundamental insights into DDK structure, control and selective activation of the MCM2-7 helicase during DNA replication. (imperial.ac.uk)
  • The six subunit Origin Recognition Complex (ORC) together with Cdc6 and Cdt1, load the MCM replicative helicase as a double hexamer around double stranded DNA at origins. (crick.ac.uk)
  • During origin firing, the MCM helicase is activated, which involves a remodeling of the MCM ring to encircle single-stranded DNA, accompanied by assembly of a stable CMG (Cdc45-MCM-GINS) complex. (crick.ac.uk)
  • We are using this to understand the mechanism of MCM helicase loading and activation, how the replisome is assembled and regulated by protein kinases and how the DNA replication machinery interfaces with other aspects of chromosome biology. (crick.ac.uk)
  • Eukaryotic origins of replication control the formation of several protein complexes that lead to the assembly of two bidirectional DNA replication forks. (wikipedia.org)
  • Collapsed forks can be rescued by homologous recombination, which restarts replication. (elifesciences.org)
  • Eukaryotic DNA replication initiates at multiple origin sites along each chromosome and terminates when replication forks (RFs) from adjacent origins converge. (elifesciences.org)
  • After origin firing, bidirectional replication forks travel until they reach termination sites. (biomedcentral.com)
  • Finally, we observed nucleosome disruption and disorganization emanating from replication origins and traveling with the elongating replication forks across the genome in S phase, likely reflecting the disassembly and assembly of chromatin ahead of and behind the replication fork, respectively. (duke.edu)
  • The controlled assembly of replication forks is critical for genome stability. (imperial.ac.uk)
  • Although known for their role in repairing dsDNA breaks, HR repair elements also stabilize and restart stalled replication forks. (biomedcentral.com)
  • Although this increased risk for TNBC could be attributed to deficiencies in DDR, novel roles for BRCA1 also include the stabilization and resolution of stalled replication forks arising from a multitude of different factors [ 5 ]. (biomedcentral.com)
  • Interestingly, a common factor in replication stress stabilization and repair after prolonged stalling of replication forks is the accumulation of non-DNA-damage-associated RAD51 and other members of the HR pathway. (biomedcentral.com)
  • This loss is accompanied with an increased expression of the histone demethylase Jmjd3 and with the recruitment of the MLL1 protein, and correlates with the expression of the Ink4a/Arf genes. (plos.org)
  • To test whether histone acetylation level regulates its replication dynamics, we induced either global hyperacetylation by pharmacological inhibition or by targeting a histone acetyltransferase to the heterochromatic region of the X chromosomes. (biomedcentral.com)
  • Our data reveal that histone acetylation level affects DNA replication dynamics of the sex chromosomes' heterochromatin and leads to a global reduction in replication fork rate genome wide. (biomedcentral.com)
  • Furthermore, we highlighted a conserved role of histone acetylation level on replication dynamics across mammalian species. (biomedcentral.com)
  • Euchromatin includes less-condensed transcriptional active regions, determined by a depletion of methylated DNA, an enrichment in specifically methylated histones such as H3K4, H3K36, H3K79 and a high level of histone acetylation [ 13 ]. (biomedcentral.com)
  • MMC also induced phosphorylation of the nuclear histone marker of DNA damage, γH2AX (a member of the H2A histone family), without induction of cell cycle entry or immediate DNA repair measured by Comet assay. (molvis.org)
  • The precise regulation of transcription, DNA replication, and DNA damage repair requires dynamic control of histone mobility orchestrated by chromatin regulation. (hhs.gov)
  • These processes are mediated by chromatin remodelers - ATP-dependent protein complexes that can reposition nucleosomes on DNA, evict nucleosomes from DNA, or exchange histone subunits, thus controlling the accessibility, flexibility, and mobility of chromatin. (hhs.gov)
  • While canonical histones H3.1 and H3.2 are synthetized and loaded during DNA replication, the histone variant H3.3 is expressed and deposited into the chromatin throughout the cell cycle. (aging-us.com)
  • Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. (arigobio.com)
  • DNA is the substrate of many cellular processes including DNA replication, transcription and chromatin remodeling. (umass.edu)
  • Genome-wide studies have provided evidence of the relationship between transcription and DNA replication timing. (umass.edu)
  • 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. (umass.edu)
  • Although recent studies in T. brucei indicate functional links among DNA replication and transcription, the underlying mechanisms remain unknown. (umass.edu)
  • We propose nucleosomes are assembled close to the replication fork followed by RNA pol II recruitment, transcription, and co-transcriptional RNA splicing. (umass.edu)
  • Together, these results provide a unified model that integrates replication, transcription and epigenetics at the INK4/ARF locus. (plos.org)
  • In higher eukaryotes, the nuclear genome is compartmentalized into distinct chromatin territories to facilitate the regulation of complex processes such as DNA repair, transcription and replication. (biomedcentral.com)
  • These findings suggest a scenario where collisions between DNA replication and transcription are frequent, leading to increased genetic variability, as seen by the increase SNP levels at chromosome subtelomeres and in DGF-1 genes containing putative origins. (biomedcentral.com)
  • Collision between replication and transcription is considered especially problematic, as each are catalyzed by large multiprotein machines, and can occur co-directionally, when the replication fork and transcription machinery are moving in the same direction, or on the leading strand and is head-on, when the fork and transcription are moving towards each other. (biomedcentral.com)
  • MMC induces DNA damage to quiescent corneal keratocytes, which remains unrepaired, resulting in abnormal cell replication and gene transcription that leads to long-term effects on corneal repair. (molvis.org)
  • Chromatin regulation involves the selective recruitment of chromatin factors to facilitate DNA repair, replication and transcription. (bvsalud.org)
  • The dynamic nature of chromatin establishes the access to the genetic material and, as a consequence, influences a large number of biological processes, such as DNA replication, repair and transcription [ 1 , 2 ]. (aging-us.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)
  • 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)
  • 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)
  • Cdc6 binding rearranges a short α-helix in the Orc1 AAA+ domain and the Orc2 WHD, leading to the activation of the Cdc6 ATPase and the formation of the three sites for the recruitment of Mcm2-7, none of which are present in ORC alone. (nature.com)
  • 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)
  • Moreover, we show that the Polycomb protein BMI1 interacts with CDC6, an essential regulator of DNA replication in eukaryotic cells. (plos.org)
  • We identified the replication licencing factor CDC6 as a new partner of the Polycomb group member BMI1. (plos.org)
  • This published article-format thesis focusses on a recently discovered primase-polymerase, and member of the archaeo-eukaryotic primase (AEP) superfamily, involved in DNA damage tolerance, known as PrimPol. (figshare.com)
  • We identify an important role for DDX5 in G 1 -S-phase progression where it directly regulates DNA replication factor expression by promoting the recruitment of RNA polymerase II to E2F-regulated gene promoters. (aacrjournals.org)
  • 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)
  • Priming of the DNA helix consists of the synthesis of an RNA primer to allow DNA synthesis by DNA polymerase α. (wikipedia.org)
  • By using an integrative approach which combines cryo-electron microscopy and X-ray crystallography, the Unit of Structural Dynamics of Macromolecules deciphered the recruitment and cooperativity mechanisms between DNA polymerase D and PCNA. (pasteur.fr)
  • PolD is an archaeal replicative DNA polymerase, which is widely distributed among Archaea and has been shown to be essential for cell viability. (pasteur.fr)
  • DDK is an S-phase-specific kinase required for replication initiation, and the DNA primase-polymerase in eukaryotes is pol α. (fsu.edu)
  • Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. (idrblab.net)
  • A research team from the Leibniz Institute for Experimental Virology (HPI) and the Centre for Structural Systems Biology (CSSB) has now shown that the formation of phase-separated compartments around viral genomes is necessary to recruit the viral DNA polymerase. (leibniz-interact.de)
  • These phase-separated pre-replication compartments are necessary to recruit viral DNA polymerase for viral genome replication. (leibniz-interact.de)
  • polymerase involved, and this in- macromolecules including DNA, 2012) . (who.int)
  • 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)
  • The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. (nature.com)
  • The results illuminate the molecular mechanism of a critical biochemical step in the licensing of eukaryotic replication origins. (nature.com)
  • In the budding yeast Saccharomyces cerevisiae , there are over 400 origins of DNA replication located on 16 chromosomes and they can function as autonomously replicating sequences (ARSs) when inserted into a plasmid 19 . (nature.com)
  • 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)
  • The putative origins identified in T. cruzi show a notable enrichment of GC content, a preferential position at subtelomeric regions, coinciding with genes transcribed towards the telomeres, and a pronounced enrichment within coding DNA sequences, most notably in genes from the Dispersed Gene Family 1 (DGF-1). (biomedcentral.com)
  • In all other eukaryotes, clear consensus sequences for origins are elusive, perhaps indicating there are no cis elements to initiate replication in most of these cells and organisms. (biomedcentral.com)
  • According to the usage, origins have been classified as constitutive (fired at same position in different cells of a population), flexible (fired stochastically in different cells) and dormant (fired as consequence of replication stress) [ 5 ]. (biomedcentral.com)
  • Expression of wild-type levels of mcm10-4A in mcm5-bob1 mutant cells resulted in severe growth and DNA replication defects, along with diminished RPA signal at replication origins. (fsu.edu)
  • The initiation of DNA replication in metazoans occurs at thousands of chromosomal sites known as origins. (elsevierpure.com)
  • Scholars@Duke publication: Cell-Cycle-Dependent Chromatin Dynamics at Replication Origins. (duke.edu)
  • Origins of DNA replication are specified by the ordered recruitment of replication factors in a cell-cycle-dependent manner. (duke.edu)
  • A cartoon of a section of chromatin in the nucleus with replication origins in three different states. (crick.ac.uk)
  • DNA replication in eukaryotic cells initiates from a large number of chromosomal sites known as origins. (crick.ac.uk)
  • GEMC1 is a 334 amino acid nuclear protein that regulates DNA replication by promoting the recruitment of Cdc45 onto replication origins. (mc1-r.com)
  • In order to restart replication, DNA damage tolerance mechanisms are required. (figshare.com)
  • Together, this work supports a role for PrimPol in repriming and restarting DNA replication following stalling at impediments, as well as identifying mechanisms involved in the recruitment and regulation of the enzyme. (figshare.com)
  • DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. (cipsm.de)
  • In conclusion, we mapped major epigenetic modifications controlling the structure of the sex chromosome-associated heterochromatin and demonstrated the occurrence of differences in the molecular mechanisms controlling the replication timing of the heterochromatic blocks at the sex chromosomes in female Microtus cabrerae cells. (biomedcentral.com)
  • The Yokomori laboratory investigates the mechanisms of chromosome structural organization and how they affect DNA repair and gene regulation in human health and disease. (uci.edu)
  • We use a variety of human cell models to understand how the deregulation of normal replication control mechanisms leads to genomic instability and whether this plays a role in cancer biology. (crick.ac.uk)
  • Given the considerable stability of the nucleosome, eukaryotic cells employ a staggering array of interconnected molecular mechanisms that locally modify the electrostatic interaction between the highly basic histones and the negatively charged DNA molecules. (aging-us.com)
  • Trinucleotide repeats are a source of genome instability, causing replication fork stalling, chromosome fragility, and impaired repair. (tufts.edu)
  • Organisms within the archaeal domain of life possess a simplified version of the eukaryotic DNA replication machinery. (pasteur.fr)
  • Euchromatin is replicated in early S-phase, when the replication machinery is present as a multitude of small replication foci that are well distributed throughout the nuclear interior. (biomedcentral.com)
  • Accumulated evidence suggests head-on collisions have a more pronounced effect on genome instability, perhaps because more extensive changes to the machinery and template are needed to resolve such conflicts [ 12 ], some of which might result in increased single-stranded DNA gaps and DNA double strand break (DSB) formation [ 13 ]. (biomedcentral.com)
  • Here, we report that the replication initiation machinery of D. melanogaster unexpectedly undergoes liquid-liquid phase separation (LLPS) upon binding DNA in vitro. (elsevierpure.com)
  • As docking units, they influence the recruitment of the transcriptional machinery, thus establishing unique gene expression patterns that ultimately promote different biological outcomes. (aging-us.com)
  • At the heart of the replisome lie the replicative DNA polymerases which catalyse synthesis of daughter DNA strands with astonishing accuracy and efficiency. (figshare.com)
  • The work presented here builds on the initial characterisation of the enzyme, which identified potential roles in the bypass of DNA damage through translesion synthesis (TLS) and repriming of replication. (figshare.com)
  • Indeed, a number of agents currently used in cancer treatment are known to target DNA synthesis. (aacrjournals.org)
  • 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)
  • Regardless of its precise form, collapse renders the fork incompetent for further DNA synthesis. (elifesciences.org)
  • In eukaryotes and archaea, PCNA stimulates processive DNA synthesis of both lagging and leading strands. (pasteur.fr)
  • Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome. (wikipedia.org)
  • The cohesin complex tethers the identical copies of each chromosome, called sister chromatids, together following DNA replication and promotes normal interphase chromosome structure and gene expression. (nih.gov)
  • Using pulse-chase replication labeling and time-lapse microscopy, we found that the heterochromatic block enriched for macroH2A/H3K27me3 of the X chromosome is replicated during mid-S-phase, prior to the heterochromatic block enriched for H3K9me3/HP1 beta, which is replicated during late S-phase. (biomedcentral.com)
  • Initiator IDRs are shown to regulate multiple functions, including chromosome recruitment, initiator-specific co-assembly, and McM2-7 loading. (elsevierpure.com)
  • Nevertheless, these enzymes are prone to stalling upon encountering DNA damage lesions and secondary structures. (figshare.com)
  • Chapter 4 focusses on the development and use of a gel-based fluorescent primase assay to assess PrimPol's ability to reprime downstream of DNA damage lesions and secondary structures. (figshare.com)
  • These results clarify the many roles of Srs2 in facilitating replication through fork-blocking hairpin lesions. (tufts.edu)
  • Describe the relationship between the systemic immunologic response, and the persistence and replication competence of Monkeypox virus (MPXV) from lesions over the course of mpox illness among people with advanced HIV. (cdc.gov)
  • Furthermore, PARP-1 abrogation leads to increased DNA resection tracks and an increase of homologous recombination in cellulo. (nature.com)
  • 2020), in which we find dissociable roles for Ino80 in YY1-associated transcriptional regulation and homologous recombination (HR) DNA repair in cortical NPCs. (hhs.gov)
  • Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. (rupress.org)
  • DNA replication is the action of DNA polymerases synthesizing a DNA strand complementary to the original template strand. (wikipedia.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)
  • 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)
  • Replicative DNA polymerases have evolved the ability to copy the genome with high processivity and fidelity. (pasteur.fr)
  • DNA polymerases (DNAPs) are the key enzymes of DNA replication and diverse DNA repair processes. (pasteur.fr)
  • Similar to other replicative DNA polymerases, the activity of PolD is strongly stimulated through its interaction with PCNA. (pasteur.fr)
  • In her current position as a biologist, her focus on human DNA polymerases continues and expands towards studying genome-wide gene expression changes in yeast strains. (nih.gov)
  • As originally proposed in 1963, cells rely on two genetic elements to duplicate their genome: the replicator, a DNA region where replication begins (now named the replication origin), and the initiator, a protein or a protein complex that recognizes the replicator [ 1 ]. (biomedcentral.com)
  • Replication processes permit copying a single DNA double helix into two DNA helices, which are divided into the daughter cells at mitosis. (wikipedia.org)
  • Agherbi H, Gaussmann-Wenger A, Verthuy C, Chasson L, Serrano M, Djabali M (2009) Polycomb Mediated Epigenetic Silencing and Replication Timing at the INK4a/ARF Locus during Senescence. (plos.org)
  • The DNA composition and transcriptional activity of these heterochromatin blocks have been studied, but little is known about their DNA replication dynamics and epigenetic composition. (biomedcentral.com)
  • Specifically, we use various DNA damaging methods, including laser microirradiation to study nucleus-wide epigenetic responses to complex DNA damage through PARP signaling and metabolic alteration. (uci.edu)
  • 4. Induces epigenetic alterations usual y arises as the cell attempts to repair the DNA damage. (who.int)
  • DNA replication is one of life's fundamental processes. (figshare.com)
  • In G1 phase of the cell cycle, many of the DNA replication regulatory processes are initiated. (wikipedia.org)
  • Further studies are needed to determine how these processes are linked and co-regulated, and how rapidly they are initiated during DNA replication. (umass.edu)
  • PROJECT SUMMARY/ABSTRACT Biological processes on nuclear DNA occur in the context of chromatin. (hhs.gov)
  • Among these regulatory processes, core and linker histones are subjected to a large pattern of posttranslational modifications (PTMs) that influence chromatin state and DNA accessibility [ 4 - 7 ]. (aging-us.com)
  • These mutations have been shown to cause diverse changes in the pattern of DNA methylation, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. (arigobio.com)
  • Thus, carcinogens nogenic are polycyclic aromatic hy- to induce DNA damage, it can be may act not only by producing DNA drocarbons and benzene, which by cal ed a genotoxicant or a genotox- damage directly but also by altering themselves are relatively inert chem- in, and if it is shown that the agent the processes that control normal ical y. (who.int)
  • The priming event on the lagging strand establishes a replication fork. (wikipedia.org)
  • Essential to these functions are RAD51 and its paralogs, each of which has a unique role in preventing replication fork collapse and restart. (biomedcentral.com)
  • In vivo confirmation was achieved through the use of a mammary epithelial cell conditional knockout mouse model before SIM2s' role in RAD51 recruitment was determined by immunoblotting. (biomedcentral.com)
  • Interestingly, loss of SIM2s was shown to result in failure of RAD51 to localize to sites of replication stress in both breast cancer cell lines and primary mammary epithelial cells. (biomedcentral.com)
  • Finally, we observed SIM2 is stabilized in response to genotoxic stress and interacts with RAD51, which is necessary for RAD51-DNA binding. (biomedcentral.com)
  • Together, these results show a role for SIM2s in the resolution of replication stress and further characterize the necessity of SIM2s for effective RAD51 loading in response to DNA damage or stress, ultimately promoting genomic integrity and thus preventing the accumulation of cancer-promoting mutations. (biomedcentral.com)
  • May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. (arigobio.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)
  • 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)
  • Here we show that in young proliferating embryonic fibroblasts (MEFs) the Polycomb Repressive Complex 2 (PRC2) member EZH2 together with PRC1 members BMI1 and M33 are strongly expressed and localized at the INK4/ARF regulatory domain (RD) identified as a DNA replication origin. (plos.org)
  • These data help explain how CDK activity controls replication initiation and suggest that replication programs are subject to higher-order levels of inter-origin organization. (elsevierpure.com)
  • During each G1 phase of two consecutive cell cycles, we observed the downstream repositioning of the origin-proximal +1 nucleosome and an increase in protected DNA fragments spanning the ARS consensus sequence (ACS) indicative of pre-RC assembly. (duke.edu)
  • Our results, therefore, place PARP-1 activation as a critical early event for DNA DSB repair activation and regulation of resection. (nature.com)
  • The cellular response to DNA damage involves an intricate network of enzymes responsible for sensing, signaling, and repairing damaged DNA, as well as the regulation of cell cycle checkpoints that collectively maintain genomic integrity 2 . (nature.com)
  • Mitomycin C (MMC) belongs to a family of anti-tumor quinolone antibiotics derived from Streptomyces caespitosus , and functions as a powerful bifunctional alkylating agent that induces DNA interstrand crosslinks (ICL). (molvis.org)
  • It was also recently shown that PARP-1 is a sensor of unligated Okazaki fragments during DNA replication 16 and cells deficient in ribonucleotide excision repair are sensitized to PARP inhibition 17 . (nature.com)
  • The predictive power of the ratio of RASGRP Hedgehog Pathway APTX gene expression not only provides a potentially important biomarker of response, it also suggests that responsive patients have underlying pathology related to abnormalities in the DNA excision repair pathway. (hsp90-inhibitors.com)
  • Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. (arigobio.com)
  • However, the exact mechanism of replication compartment biogenesis remains unknown. (leibniz-interact.de)
  • The replisome is responsible for copying the entirety of genomic DNA in each proliferative cell. (wikipedia.org)
  • However, the replisome can be stalled by depletion of nucleotide pools or barriers on the template, such as DNA damage, secondary structures or protein complexes [ 11 ]. (biomedcentral.com)
  • 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)
  • Using biophysical, biochemical, and cellular approaches, this paper identifies the mechanism by which PrimPol is recruited to reprime replication. (figshare.com)
  • Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. (arigobio.com)
  • As we previously hypothesized ( 6 ), co-virus-induced cellular damage resulting in high levels of cellular division and differentiation may stimulate HBoV reactivation and replication, as has been shown for polyomavirus following induced kidney damage in newborn mice ( 8 ). (cdc.gov)
  • Specialized helicases play an important role in unwinding DNA structures to maintain genome stability. (tufts.edu)
  • The DNA replication process is highly regulated both spatially and temporally, resulting in the changing pattern of replication structures throughout S-phase. (biomedcentral.com)
  • Upon activation, PARP-1 synthesizes a structurally complex polymer composed of ADP-ribose units that facilitates local chromatin relaxation and the recruitment of DNA repair factors. (nature.com)
  • De Murcia and colleagues provided the first evidence implicating PARP-1 in DNA repair by demonstrating that PARP-1-deficient mice are highly sensitive to γ-irradiation 21 . (nature.com)
  • DNA repair. (tufts.edu)
  • The purpose of this study was to determine the acute and long-term effects of mitomycin C (MMC) on quiescent rabbit corneal keratocytes regarding cell proliferation, myofibroblast differentiation and DNA repair. (molvis.org)
  • Notably, impaired DNA repair is the driver of neuroanatomical phenotypes following Ino80 deletion, thus demonstrating that this underexplored role of chromatin can effect neurodevelopmental consequences. (hhs.gov)
  • Importantly, Ino80's DNA repair function is not unique among chromatin remodelers. (hhs.gov)
  • In this application, we seek to investigate a potentially wider role of chromatin remodeling in DNA damage and repair in NPCs. (hhs.gov)
  • With many potential causes of replication stress, there is no singular replication stress repair pathway. (biomedcentral.com)
  • Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. (idrblab.net)
  • In Eukarya and Archaea, their processivity is greatly enhanced by binding to the proliferative cell nuclear antigen (PCNA) that encircles the DNA. (pasteur.fr)
  • In their work, the Unit of Structural Dynamics of Macromolecules presented the structure of the DNA-bound PolD-PCNA complex from P. abyssi at 3.77 Å using an integrative structural biology approach, combining cryo-EM, X-ray crystallography, protein-protein interaction measurements and activity assays. (pasteur.fr)
  • They infered that the C-terminal PIP-box, plays a dual role in binding either PCNA or primase, and could be a master switch between an initiation phase and a processive phase during replication. (pasteur.fr)
  • Examples of direct-acting elec- all have an impact on the outcome trophilic carcinogens are formalde- The term "genotoxic" refers to an of this proces s (Arana and Kunkel, hyde, sulfur mustard, and ethylene agent that induces DNA damage, 2010) . (who.int)
  • Remarkably, inhibition of PARP-1 leads to hyperresected DNA DSBs. (nature.com)
  • These data indicate that the effect of MMC on corneal scarring and haze is related to the generation of DNA ICLs leading to defective cell replication and gene expression. (molvis.org)
  • Upon senescence, Jmjd3 is overexpressed and the MLL1 protein is recruited to the locus provoking the dissociation of Polycomb from the INK4/ARF locus, its transcriptional activation and its replication during early S-phase. (plos.org)
  • This type of heterochromatin is replicated during the mid-S-phase, when the replication foci become larger and are located around the nucle(ol)ar periphery. (biomedcentral.com)
  • SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
  • Our results show that phase separation is crucial for the formation of pre-replication compartments and viral DNA replication. (leibniz-interact.de)
  • The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. (cipsm.de)
  • PARP-1 acts as a highly sensitive sensor for DNA damage and rapidly produces PAR at newly generated DNA DSBs. (nature.com)
  • The dynamic turnover of PAR within seconds to minutes is executed by poly(ADP-ribose) glycohydrolase, the main PAR-degrading enzyme, which possesses both endoglycosidic and exoglycosidic activities, thereby enabling a new round of DNA damage signaling 14 . (nature.com)
  • DNA damage was evaluated in both cultured keratocytes and live rabbit eyes following treatment with MMC. (molvis.org)
  • We aim to understand how the 46 chromosomes in our cells are precisely duplicated in each cell cycle, how this process responds to DNA damage and how it is misregulated in cancer. (crick.ac.uk)
  • This click chemistry reaction yields a stable covalent linkage, facilitating streptavidin capture of cross-linked biotinylated DNA-protein complexes. (umass.edu)
  • Consistent with this, PARP-1 activity increases the rate of recruitment of the MRE11-RAD50-NBS1 (MRN) complex 10 and stimulates Ku binding in Dictyostelium 22 . (nature.com)