Replication fork replication factors. Medical search. Frequent questions

By exogenously modulating its activity, we demonstrate that PP1α is required to maintain CHK1 in a dephosphorylated state and, more importantly, that it is responsible for the accelerated replication fork progression in Spi1/PU.1-overexpressing cells. (oncotarget.com)
Resolution of superhelical tension is critical to ensure replication fork progression and avoid chromosome damage. (mpg.de)
DNA replication and DSB repair each occur in the context of chromatin, which must be reorganized for all transactions on DNA, including replication fork progression, DSB detection, and recruitment of DNA repair factors. (hhs.gov)
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)
For instance, DNA replication and DNA damage checkpoints delay cell cycle progression until each chromosome is fully replicated and physically intact. (rupress.org)
Chromatin assembly and the establishment of sister chromatid cohesion are intimately connected to the progression of DNA replication forks. (cell-stress.com)

Proliferating Cell Nuclear Antigen (PCNA), which is a homotrimeric ring-structure complex plays an important role in coordinating the replication fork-associated process during the DNA damage response and replication process. (nih.gov)
The initial loading of PCNA on DNA to initiate each Okazaki fragment synthesis as well as whole replication process was catalyzed by the Replication factor C (RFC) complex. (nih.gov)
Previously, we showed that ATAD5 protein, which is a mammalian homolog of yeast Elg1 protein, regulates the level of PCNA in chromatin during normal DNA replication as well as ubiquitylated PCNA in response to DNA damage. (nih.gov)
We are currently investigating impact of these variants in regulation the level of PCNA in chromatin, the level of ubiquitylation of PCNA and other consequences in DNA metabolism including replication kinetics, recombination, and mutagenesis. (nih.gov)
Loads PCNA onto primed templates regulating velocity, spacing and restart activity of replication forks. (nih.gov)
CHTF18 (MIM 613201), CHTF8 (MIM 613202), and DSCC1 are components of an alternative replication factor C (RFC) (see MIM 600404) complex that loads PCNA (MIM 176740) onto DNA during S phase of the cell cycle (Merkle et al. (nih.gov)
The Rad17-RFC and 9-1-1 complexes are structurally similar to the RFC (replication factor C) clamp loader and PCNA sliding clamp, respectively, and similar mechanisms are thought to be used during loading of the 9-1-1 complex and PCNA. (reactome.org)
However, how eukaryotic Pol δ achieves processive DNA synthesis and how it cooperates with PCNA and other factors during Okazaki fragment processing remains unknown. (nature.com)
PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. (bvsalud.org)

Replicative repair of interstrand crosslinks (ICL) generated by platinum chemotherapeutics is orchestrated by the Fanconi anemia (FA) repair pathway to ensure resolution of stalled replication forks and the maintenance of genomic integrity. (nki.nl)
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)

HR is important for the accurate repair of DNA double-strand breaks and DNA interstrand crosslinks, and it restarts stalled or collapsed replication forks. (researchwithrutgers.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)
During replication, separation of the two daughter-strand templates by the helicase leads to overwinding and the formation of positive supercoils ahead of the replication fork. (mpg.de)
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)
To execute these functions, the replisome contains a helicase, DNA polymerases, as well as several associated factors that together make up the replication fork (see Figure 1). (advancedsciencenews.com)
Eukaryotic TFIIH basal transcription factor complex helicase XPB subunit. (embl.de)
An ATP-dependent 3'-5' DNA helicase which is a component of the core-TFIIH basal transcription factor, involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. (embl.de)
In vitro studies indicate that loading is preferred onto DNA substrates containing ssDNA gaps that presumably resemble structures found upon replication fork stalling and DNA polymerase/helicase uncoupling. (reactome.org)
Nick translation by the strand displacement action of DNA polymerase δ, coupled with the nuclease action of FEN1, results in processive RNA degradation until a proper DNA nick is reached for closure by DNA ligase I. In the event of excessive strand displacement synthesis, other factors, such as the Dna2 nuclease/helicase, are required to trim excess flaps. (wustl.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)
These are a protein annotated as a Replication Factor C subunit (Tb927.10.7990), and a protein of unknown function (Tb927.3.5370). (umass.edu)
This multi-subunit complex is formed by two SMC proteins (Smc1 and Smc 3) and an alpha-kleisin (Scc1) to which the accessory factors Scc3, Pds5 and Wpl1 associate. (advancedsciencenews.com)
May couple DNA replication to sister chromatid cohesion through regulation of the acetylation of the cohesin subunit SMC3. (nih.gov)
CHAF1B is the p60 subunit of the chromatin assembly factor (CAF1) complex, which is responsible for assembly of histones H3.1/H4 heterodimers at the replication fork during S phase. (telethonkids.org.au)

Cohesion of sister chromatids, an important aspect during replication, is mediated via cohesin. (advancedsciencenews.com)
Collectively, our results suggest that the deposition by CAF-1 of newly-synthesized H3-H4 histones during DNA replication creates a chromatin environment that favors sister chromatid cohesion and maintains genome integrity. (cell-stress.com)
The chromosomal cohesin complex establishes sister chromatid cohesion during S phase, which forms the basis for faithful segregation of DNA replication products during cell divisions. (crick.ac.uk)
Cohesion establishment is defective in the absence of either of three non-essential Saccharomyces cerevisiae replication fork components Tof1-Csm3 and Mrc1. (crick.ac.uk)
Here, we investigate how these conserved factors contribute to cohesion establishment. (crick.ac.uk)
By modulating each of these functions independently, we rule out that one of these known replication roles explains the contribution of Tof1-Csm3 and Mrc1 to cohesion establishment. (crick.ac.uk)
Our findings open the possibility that a series of physical interactions between replication fork components and cohesin facilitate successful establishment of sister chromatid cohesion during DNA replication. (crick.ac.uk)

Figure 1: Schematic representation of the eukaryotic replication fork. (advancedsciencenews.com)

Chromosome replication is performed by a large multisubunit assembly, known as the replisome, which couples the unpackaging of parental DNA with the synthesis of new daughter strands. (mpg.de)
Figure 2: Cohesin function during the chromosome replication cycle. (advancedsciencenews.com)
It is well known that the products of chromosome replication are paired to ensure that the sisters segregate away from each other during mitosis. (rupress.org)
Thus, the products of chromosome replication (sister chromatids) generated during S-phase must be identified over time until mitosis when sisters associate with the mitotic spindle and segregate away from each other into the newly forming daughter cells. (rupress.org)
Long gaps between active replication origins probably occur frequently during chromosome replication, but little is known about how cells cope with them. (nyu.edu)

The source of genomic instability on iPSC remains unresolved, although several evidence suggest that it could be linked to replication stress (RS), a type of DNA damage occurring at ML335 stalled replication forks and limited by the ataxia telangiectasia and Rad3-related (ATR) and checkpoint kinase 1 (CHK1) kinases9. (researchassistantresume.com)
In the absence of CTF4 , CAF-1 is essential for viability in cells experiencing replication problems, in cells lacking functional S-phase checkpoint or functional spindle checkpoint, and in cells lacking DNA repair pathways involving homologous recombination. (cell-stress.com)
ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage. (elsevierpure.com)
Tof1-Csm3 and Mrc1 serve known roles during DNA replication, including replication checkpoint signaling, securing replication fork speed, as well as recruiting topoisomerase I and the histone chaperone FACT. (crick.ac.uk)

However, replication restart is relatively slow and, therefore, replication termination may frequently occur by an active fork converging on a collapsed fork. (elifesciences.org)
TP53 inhibition allows LINE-1 + cells to grow, and genome-wide-knockout screens show that these cells require replication-coupled DNA-repair pathways, replication-stress signaling and replication-fork restart factors. (nih.gov)
Blocking PFKFB3 activity disrupts the assembly of key FA repair factors and consequently prevents fork restart. (nki.nl)
PriA protein is one of seven proteins that make up the restart primosome, an apparatus that promotes assembly of replisomes at recombination intermediates and stalled replication forks. (embl.de)
Although known for their role in repairing dsDNA breaks, HR repair elements also stabilize and restart stalled replication forks. (biomedcentral.com)
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)

TIPIN has been shown to interact with Replication protein A1. (wikipedia.org)
Chromosomal DNA replication involves several complex protein complexes. (advancedsciencenews.com)
Viral DNA synthesis involves a DNA repair enzyme, the uracil-DNA glycosylase D4 linked to the structural protein A20 forming the processivity factor, which in turn binds to E9 forming the complex required for processive DNA synthesis. (biorxiv.org)
This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted. (elsevierpure.com)

While the double-helical structure of duplex DNA is advantageous for the storage and maintenance of genetic information, it poses major challenges during essential cellular processes, such as transcription and replication, when the information-rich DNA bases must be accessed. (mpg.de)
We examine the impact that processes such as transcription and replication have on genome stability. (birmingham.ac.uk)
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)

The controlled assembly of replication forks is critical for genome stability. (imperial.ac.uk)
Here, we show loss of SIM2s decreases replication fork stability, leading to fork collapse in response to genotoxic stress. (biomedcentral.com)
With the increased instance of highly invasive breast cancer in individuals with mutations in BRCA, the identification of other factors that mimic the ability of BRCA1 to maintain genomic stability would expand our repertoire of oncogenic markers and increase our ability to design targeted treatments for breast cancer patients. (biomedcentral.com)
Novel factors of chromatin stability. (cell-stress.com)

We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks. (oncotarget.com)

The results illuminate the molecular mechanism of a critical biochemical step in the licensing of eukaryotic replication origins. (imperial.ac.uk)
Our findings demonstrate that LINE-1 expression creates specific molecular vulnerabilities and reveal a retrotransposition-replication conflict that may be an important determinant of cancer growth. (nih.gov)
In doing so they provide a molecular perspective on how replication machineries deal with cohesin to achieve a stable association of nascent sister chromatids. (advancedsciencenews.com)
They discovered that the exonuclease, the 'proofreading' portion of the polymerase that ensures copy accuracy, played a key role, a new, rare insight into the largely unknown molecular mechanism behind fork reversal. (groundrushairsports.com)
Garg, P & Burgers, PMJ 2005, ' DNA polymerases that propagate the eukaryotic DNA replication fork ', Critical Reviews in Biochemistry and Molecular Biology , vol. 40, no. 2, pp. 115-128. (wustl.edu)
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)

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)
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 prototype of DEAD-box proteins is the translation initiation factor eIF4A. (embl.de)
The year 2022 was marked by the mpox outbreak caused by human monkeypox virus (MPXV), which is about 98 % identical to vaccinia virus (VACV) at the sequence level regarding the proteins involved in DNA replication. (biorxiv.org)

WASp modulates RPA function on single-stranded DNA in response to replication stress and DNA damage. (us.es)

The 9-1-1 complex has also been found to interact with base excision repair factors human DNA polymerase beta, flap endonuclease FEN1, and the S. pombe MutY homolog (SpMYH), indicating that 9-1-1 also plays a direct role in DNA repair. (reactome.org)
We present the strategy for the production of the VACV DNA polymerase holoenzyme composed of the E9 polymerase associated with its co-factor, the A20-D4 heterodimer, which led to the 3.8 Å cryo-electron microscopy (cryo-EM) structure of the DNA-free form of the holoenzyme. (biorxiv.org)
For the first time, they showed that the 'proofreading' portion of the DNA replicating enzyme polymerase epsilon ensured safe termination of replication at damaged portions of the DNA strand, ultimately saving DNA from severe damage. (groundrushairsports.com)
This suggests that PARP and the polymerase epsilon exonuclease work together to trigger fork reversal. (groundrushairsports.com)
2023). The proofreading exonuclease of leading-strand DNA polymerase epsilon prevents replication fork collapse at broken template strands. (groundrushairsports.com)

Regardless of its precise form, collapse renders the fork incompetent for further DNA synthesis. (elifesciences.org)

By reconstituting the S. Cerevisiae replication machinery at the single complex level we are able to study critical transient intermediates formed during chromatin replication. (mpg.de)

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. (imperial.ac.uk)
To address this issue, we deleted replication origins from S. cerevisiae chromosome III to create chromosomes with long interorigin gaps and identified mutations that destabilize them [originless fragment maintenance (Ofm) mutations]. (nyu.edu)

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)

While the causes of RS ML335 are still not fully understood, some of the sources include insufficient levels of deoxynucleotides10, reduced levels of replication factors11, or mutations in DNA repair and replication factors (reviewed in ref. 9). (researchassistantresume.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)

Collapsed forks can be rescued by homologous recombination, which restarts replication. (elifesciences.org)
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)

Following replication, cohesin embraces both sister chromatids and holds them together until mitosis. (advancedsciencenews.com)

The precise regulation of transcription, DNA replication, and DNA damage repair requires dynamic control of histone mobility orchestrated by chromatin regulation. (hhs.gov)
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)

We seek to define the operating principles that guide replisome function and understand how replisomes recognize and process obstacles encountered on parental chromosomes such as DNA lesions, unfavorable topological structures, and architectural factors. (mpg.de)
The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. (imperial.ac.uk)
Deletion of the H3K56 acetylase and downstream chromatin assembly factors suppressed the Ofm phenotype of hst3, indicating that persistence of H3K56Ac-containing chromatin is deleterious for the maintenance of ORIΔ chromosomes, and experiments with synchronous cultures showed that it is replication of H3K56Ac-containing chromatin that causes chromosome loss. (nyu.edu)

Upon loading, the 9-1-1 complex can recruit Chk1 onto sites of replication fork uncoupling or DNA damage. (reactome.org)
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)

These results identify a novel pathway by which an oncogene influences replication in the absence of DNA damage. (oncotarget.com)
With such a pivotal role in the maintenance of genomic integrity, furthering our understanding of this pathway through the discovery of new factors involved in HR is important. (biomedcentral.com)
With many potential causes of replication stress, there is no singular replication stress repair pathway. (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)

The dynamic events that underlie the disassembly and reassembly of nucleosomes during replication remains a long-standing puzzle in chromosome biology. (mpg.de)
Nucleosomes pose a two-fold problem for the replication machinery. (mpg.de)
We propose nucleosomes are assembled close to the replication fork followed by RNA pol II recruitment, transcription, and co-transcriptional RNA splicing. (umass.edu)
H3K56Ac-containing nucleosomes are preferentially assembled into chromatin behind replication forks. (nyu.edu)

Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination. (elifesciences.org)

This results in an incapacity to replicate cells to progress through S-phase, an accumulation of DNA damage in replicating cells, and fork collapse. (nki.nl)

Eukaryotic DNA replication initiates at multiple origin sites along each chromosome and terminates when replication forks (RFs) from adjacent origins converge. (elifesciences.org)
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)

DNA is the substrate of many cellular processes including DNA replication, transcription and chromatin remodeling. (umass.edu)
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)
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)

Although recent studies in T. brucei indicate functional links among DNA replication and transcription, the underlying mechanisms remain unknown. (umass.edu)
Cellular factors which play role in host defense mechanisms against HIV were identified and their role in HIV induced inflammation was established. (europa.eu)
Our research is defining the normal mechanisms of DNA replication and repair, with the aim of understanding how it is deregulated in cancer cells. (birmingham.ac.uk)

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)

Perturbation in the replication-stress response (RSR) and DNA-damage response (DDR) causes genomic instability. (us.es)

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)

Further analysis was conducted via immunostaining to determine the effect loss of SIM2s has on factor recruitment. (biomedcentral.com)

Tb927.10.7990 proved to be essential since its silencing caused a growth defect and impaired DNA replication. (umass.edu)

A major known function of the 9-1-1 complex is to recruit Chk1 to stalled replication forks for activation by ATR. (reactome.org)

These unique experimental approaches will clarify the distinct roles of key factors in coordinating inheritance and deposition. (mpg.de)
At least two classes of factors are critical for sister chromatid pairing: structural cohesins and deposition factors. (rupress.org)
We find that CAF-1 deficient cells as well as cells affected in newly-synthesized H3-H4 histones deposition during DNA replication exhibit a severe negative growth with ctf4 ∆ mutant. (cell-stress.com)

however, it can generally be defined as a slowing or stalling of the replication fork complex [ 6 ]. (biomedcentral.com)

Exploring cohesin and replisome interactions during DNA replication. (advancedsciencenews.com)
As cohesin is already present before the arrival of the replication fork, the question arises how cohesin interacts with the replisome. (advancedsciencenews.com)
Figure 3: Different models showing the intefacing between chromatin-bound cohesin and the replication fork. (advancedsciencenews.com)

Another is 'fork reversal', where the replication process is reversed, preventing the single-strand nicks turning into DSBs in the first place. (groundrushairsports.com)

In eukaryotes, DNA replication is separated in time from chromosome segregation. (rupress.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)

Results The expression of reprogramming factors generates RS First, we evaluated to what extent DNA damage occurred during reprogramming by analysing the levels of H2AX phosphorylation (H2AX). (researchassistantresume.com)

Here, we identify novel regulation of FA repair by the cancer-associated glycolytic enzyme PFKFB3 that has functional consequences for replication-associated ICL repair and cancer cell survival. (nki.nl)
However, progress toward understanding the regulation of these factors has been slow. (biomedcentral.com)

Initial analysis of the effect loss of SIM2s has on replication stress resolution was conducted using DNA combing assays in established breast cancer cell lines. (biomedcentral.com)

Anatomy18

Organisms24

Diseases5

Chemicals and Drugs110

Analytical, Diagnostic and Therapeutic Techniques and Equipment29

Phenomena and Processes84

Information Science3

Health Care2

Progression6

PCNA9

Resolution of stalled replication forks2

Stalled or collapsed replication forks1

Helicase8

Subunit5

Cohesion7

Eukaryotic replication fork1

Chromosome replication5

Checkpoint4

Restart6

Protein4

Transcription and replication3

Stability4

Increased replication fork speed1

Molecular6

Proteins6

Response to replication stress1

Polymerase5

Synthesis1

Chromatin replication1

Cerevisiae2

Mitotic1

Mutations2

Recombination2

Sister chromatids1

Histone4

Chromosomes3

Sites of replication2

Pathway4

Nucleosomes4

Termination1

Collapse1

Origins2

Processes3

Mechanisms3

Machinery1

Genomic instability1

Initiation2

Recruitment1

Essential1

CHK11

Deposition3

Complex1

Cohesin3

Strand1

Eukaryotes1

Epigenetic1

Damage1

Regulation2

Stress1