Inhibitor of DNA replicationFork progressionProgressionInhibitionProposed hallmaPolymerase InhibitorInducesInstabilityCHK1ForksMitosisFragileDSBsDissectMitoticChromatinSynthesisChromosomesRecombinationTranscriptionOriginsIndicativeEnzymesInitiationDeletionDemonstrateIntegrityVitroReplicateStressHumansPromotesCyclinRepairCellsWorkOriginConcentrationSitesActivityMember
Inhibitor of DNA replication2
- Quantitative fluorescence microscopy and transient transfection in the presence of aphidicolin, an inhibitor of DNA replication, show that CENP-A can assemble into centromeres in the absence of DNA replication. (rupress.org)
- Aphidicolin, an inhibitor of DNA replication, blocks the TPA-induced differentiation of a human megakaryoblastic cell line, MEG-O1. (neb.com)
Fork progression3
- Investigating the mechanism of synthetic lethality, we reveal that CHK1 inhibition in IGF-1R depleted or inhibited cells further downregulated RRM2, reduced dNTP supply and profoundly delayed replication fork progression. (nature.com)
- High speed of fork progression induces DNA replication stress and genomic instability. (nature.com)
- R-loops were linked to head-on TRCs and proposed to obstruct replication fork progression. (stanford.edu)
Progression2
- In this study, we show that inhibition of Plk1 impairs DNA replication and results in slow S-phase progression in cultured cancer cells. (uky.edu)
- In the p53 pathway, the gene activates its transcriptional target p21 which is an inhibitor of cyclin / cdk2 as they work for the progression of replication and inactivates RB. (ijpsr.com)
Inhibition3
- We recently reported that genetic or pharmacological inhibition of insulin-like growth factor receptor (IGF-1R) slows DNA replication and induces replication stress by downregulating the regulatory subunit RRM2 of ribonucleotide reductase, perturbing deoxynucleotide triphosphate (dNTP) supply. (nature.com)
- The mechanism of this effect appears to involve a conversion of sublethal SSBs into lethal DSBs during DNA replication due to the inhibition of base excision repair by the drug. (oncotarget.com)
- Both transcription inhibition in early S-phase and RNaseH1 overexpression reduced MiDAS in BRCA2-deficient cells, indicating that transcription-replication conflicts (TRCs) and R-loops are the source of MiDAS. (ox.ac.uk)
Proposed hallma1
- Changes in the timing of replication, origin usage and replication rate are indicative of DNA replication stress, a proposed hallmark of cancer that causes genome instability. (lancs.ac.uk)
Polymerase Inhibitor1
- The adozelesin-induced RPA hyperphosphorylation can be blocked by the replicative DNA polymerase inhibitor, aphidicolin, overwatch 2 aimbot hack download that adozelesin-triggered cellular DNA damage responses require active DNA replication forks. (aquagadget.com)
Induces1
- This induces double-strand breaks in the DNA, inhibiting DNA replication. (wikipedia.org)
Instability1
- Transcription-replication collisions (TRCs) are crucial determinants of genome instability. (stanford.edu)
CHK15
- Exogenous RRM2 expression rescued hallmarks of replication stress induced by co-inhibiting IGF with CHK1 or WEE1, identifying RRM2 as a critical target of the functional IGF:CHK1 and IGF:WEE1 interactions. (nature.com)
- The focus of this study is the role of protein kinase Chk1 and the phosphatase Cdc25A in the DNA replication checkpoint. (vt.edu)
- Chk1 is also transiently activated at the MBT in Xenopus laevis embryos, even when there is no block to DNA replication or damaged DNA. (vt.edu)
- Embryos treated with aphidicolin, resulting in a halted replication fork and therefore a reduced DNA concentration, were tested for Chk1 activation and Cdc25A degradation. (vt.edu)
- We observed a mean two.6-fold enhance in fork density in aphidicolin-treated extracts when Chk1 was inhibited (Fig 3C). (epigenetics-modulation-frontier.com)
Forks1
- Combining EM and immuno-labeling on locus-specific head-on TRCs in bacteria, we observed the frequent accumulation of DNA:RNA hybrids behind replication forks. (stanford.edu)
Mitosis3
- Another reason synchrony is important is the control for amount of DNA content, which varies at different parts of the cell cycle based on whether DNA replication has occurred since the last round of completed mitosis and cytokinesis. (wikipedia.org)
- In Xenopus laevis, early embryonic development consists of twelve rapid cleavage cycles between DNA replication (S) and mitosis (M) without checkpoints or gap phases. (vt.edu)
- Aberrant replication causes cells lacking BRCA2 to enter mitosis with under-replicated DNA, which activates a repair mechanism known as mitotic DNA synthesis (MiDAS). (ox.ac.uk)
Fragile4
- Exposure of lymphoblastoid cells to WTC particulate matter led to dysregulation of DNA replication at common fragile sites in vitro. (nature.com)
- FANCD2 facilitates replication through common fragile sites. (nature.com)
- High-resolution profiling revealed that these sites are different from MiDAS at aphidicolin-induced common fragile sites in that they map to genomic regions replicating in the early S-phase, which are close to early-firing replication origins, are highly transcribed, and display R-loop-forming potential. (ox.ac.uk)
- Chromosomal common fragile sites (CFSs) are unstable genomic regions that break under replication stress and are involved in structural variation. (psu.edu)
DSBs1
- Niraparib also sensitized tumor cells to H 2 O 2 and converted H 2 O 2 -induced single strand breaks (SSBs) into DSBs during DNA replication. (oncotarget.com)
Dissect2
- These data demonstrate the potential for cell free DNA replication assays to be combined with DNA combing to dissect replication parameters and characterise DNA replication stress in future studies. (lancs.ac.uk)
- To dissect the mechanism pertinent to this observation, we showed that Orc2-S188 phosphorylation associates with DNA replication origin and that cells expressing Orc2-S188A mutant fail to maintain the functional pre-replicative complex (pre-RC) under DNA replication stress. (uky.edu)
Mitotic2
- During the mitotic mammalian cell cycle cells faithfully replicate their DNA utilizing multiple DNA replication sites known as origins of replication. (lancs.ac.uk)
- Mitotic DNA synthesis is caused by transcription-replication conflicts in BRCA2-deficient cells. (ox.ac.uk)
Chromatin3
- Thus, unlike most genomic chromatin, histone synthesis and assembly are uncoupled from DNA replication at the kinetochore. (rupress.org)
- Uncoupling DNA replication from CENP-A synthesis suggests that regulated chromatin assembly or remodeling could play a role in epigenetic centromere propagation. (rupress.org)
- Such mutations are thought to promote tumorigenesis by disturbing transcriptional homeostasis due to impairment of chromatin remodeling for transcription, DNA damage repair, DNA replication and chromatin segregation. (justia.com)
Synthesis2
- Replication is catalysed by processive replication enzymes known as DNA polymerases and is limited to the synthesis phase (S phase) of the cell cycle. (lancs.ac.uk)
- Cells expressing the unphosphorylatable mutant (S188A) of Orc2 had defects in DNA synthesis under stress, suggesting that this phosphorylation event is critical to maintain DNA replication under stress. (uky.edu)
Chromosomes2
- In this work, we have directly examined replication timing of the prekinetochore domain of human chromosomes. (rupress.org)
- Bacteria have a single replication origin but organisms with large chromosomes, such as humans, need many origins. (ukri.org)
Recombination10
- Topoisomerases are nuclear enzymes that modify the topological state of DNA and participate in fundamental metabolic processes such as replication, transcription, repair, recombination, and chromosome segregation (1) . (aacrjournals.org)
- Cells without origins use a process called recombination to start DNA replication. (ukri.org)
- We found that recombination starts DNA replication at random locations on the chromosome, instead of at specific origins. (ukri.org)
- But if this alternative mode of DNA replication using recombination is more efficient, why have origins at all? (ukri.org)
- This means that Haloferax mediterranei needs origins, while Haloferax volcanii can instead use recombination to start DNA replication. (ukri.org)
- At the same time, we will examine the consequences of using recombination to start DNA replication. (ukri.org)
- Haloferax volcanii can use recombination to start DNA replication but this may be hazardous. (ukri.org)
- We have shown that recombination-dependent replication also operates in archaea. (ukri.org)
- In the archaeon Haloferax volcanii, deletion of all origins or genes encoding initiator proteins leads to the initiation of replication by recombination - strikingly, this also leads to accelerated growth. (ukri.org)
- If recombination alone can efficiently initiate the replication of a cellular genome, what purpose do origins serve and why they have evolved? (ukri.org)
Transcription1
- Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids. (stanford.edu)
Origins6
- Replication proceeds bi-directionally from a minority of potential origins licensed for replication by a variety of replication factor proteins. (lancs.ac.uk)
- These data suggest that Ap4A can inhibit the firing of replication origins through disruption of replication complex assembly. (lancs.ac.uk)
- From Comparative Genomics to Comparative Genetics - What is Required for Life Without DNA Replication Origins? (ukri.org)
- This is called DNA replication and begins at specific sites on the chromosome called origins. (ukri.org)
- When origins are deleted from eukaryotes or bacteria, DNA replication is prevented and cells die. (ukri.org)
- DNA replication initiates at origins, which serve as binding sites for initiator proteins that recruit the replicative machinery. (ukri.org)
Indicative1
- These effects resulted in significant accumulation of unreplicated single-stranded DNA and increased cell death, indicative of replication catastrophe. (nature.com)
Enzymes2
- Haloferax volcanii comes from the Dead Sea, we chose it because the enzymes that carry out DNA replication in archaea are similar to those in eukaryotes, such as human cells. (ukri.org)
- These enzymes have roles in DNA repair, as well as DNA replication. (tocris.com)
Initiation1
- Here using an in vitro cell-free DNA replication system we analyse the interplay between Ciz1 and cyclin A/CDK2 in regulation of the initiation phase of DNA replication. (lancs.ac.uk)
Deletion1
- The DNA mismatch repair (MMR) system is involved in the correction of base/base mismatches and insertion/deletion loops arising during replication. (aacrjournals.org)
Demonstrate1
- These results demonstrate that independent of DNA replication, the TOP1 clearable complex is ubiquitinated and destroyed in cells treated with antitumor drugs that block the religation step of the TOP1 reaction. (tmu.edu.tw)
Integrity2
- Our study suggests a novel role of Plk1 in facilitating DNA replication under conditions of stress to maintain genomic integrity. (uky.edu)
- This makes the error rate during DNA replication very low, hence maintaining the integrity of the genome. (tocris.com)
Vitro1
- We have identified origin recognition complex 2 (Orc2), a member of the DNA replication machinery, as a Plk1 substrate and have shown that Plk1 phosphorylates Orc2 at Ser188 in vitro and in vivo. (uky.edu)
Replicate1
- Cytological analysis of DNA replication further demonstrated that centromeres replicate asynchronously in parallel with numerous other genomic regions. (rupress.org)
Stress1
- Cell senescence can be a result of the exposure to stress such as oxidative stress, epigenomic damage or DNA damage, or it can be due to telomere shortening is also known as end replication problem. (ijpsr.com)
Humans1
- 5-ethyl-2'-deoxyuridine (edu) is a potent and selective inhibitor of the replication of herpes simplex virus type 1 (hsv-1) and 2 (hsv-2), which is currently being pursued for the topical treatment of hsv-1 and hsv-2 infections in humans. (liverpool.ac.uk)
Promotes1
- ALT, however, promotes telomere elongation using homology directed DNA damage repair via break induced replication [ 1 - 4 ]. (oncotarget.com)
Cyclin1
- This demonstrates that Ciz1 modulates and enhances the activity of cyclin A-CDK2 in cell free DNA replication assays and that Ciz1 increases the permissive CDK range that can promote DNA replication. (lancs.ac.uk)
Repair1
- ALT was recently described to resemble break-induced replication (BIR), a specific homology directed repair pathway utilized to repair one-sided DNA double-stranded breaks that are often generated following replication fork collapse [ 4 ]. (oncotarget.com)
Cells3
- Here we find that the replication fork progresses at 1.3kbp/min in mouse fibroblast cells, consistent with other studies, and quantify replication fork stalling by replication inhibitor aphidicolin. (lancs.ac.uk)
- Cancer cells often have mutations in the genes that control DNA replication and polyploidy is a common feature of cancer. (ukri.org)
- Another consequence of uncoordinated replication is that cancer cells grow faster than ordinary cells. (ukri.org)
Work1
- Replication of this work using a larger sample size will help us to differentiate true positive findings. (biomedcentral.com)
Origin3
- When this is attempted, a dormant replication origin becomes active. (ukri.org)
- This is similar to the faster growth we observe with origin-less Haloferax volcanii, which use an alternative mode of DNA replication. (ukri.org)
- Our results contrast with those obtained in Haloferax mediterranei, where origin-dependent replication is strictly required. (ukri.org)
Concentration2
- Detectable myxoma virus replication was inhibited at a drug concentration of 100 micrograms/ml. (curehunter.com)
- Fibroma virus replication was inhibited at a concentration of 500 micrograms/ml. (curehunter.com)
Sites1
- Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile sites, using multiple logistic regression. (psu.edu)
Activity1
- Finally, the multi-Ub conjugates of TOP1 were observed whether or not aphidicolin was included in cotreatment with CPT, indicating that replication fork activity was not involved in making TOP1 a substrate for ubiquitination. (tmu.edu.tw)
Member1
- Our research on DNA replication was carried out in Haloferax volcanii, a member of the archaea. (ukri.org)