• Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. (nih.gov)
  • Replication blockages activate the ATR kinase which, in turn, activates the downstream effector kinase Chk1 through the mediator protein, Claspin. (caltech.edu)
  • We characterized Xenopus Claspin as a kinase substrate of DDK which forms a stable nuclear complex with Cdc7 and Drf1 under both arrested and unperturbed replication conditions. (caltech.edu)
  • Initiation of DNA replication during the mitotic cell cycle requires the activation of a cyclin-dependent protein kinase (CDK). (ox.ac.uk)
  • Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
  • In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.com)
  • Decreased expression of six RNA species was seen at various time points in all cell strains analyzed, these were: plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), a putative mitotic checkpoint kinase (BUB1) and a gene of unknown function (GenBank accession number AI859865). (cdc.gov)
  • We propose that SMC-5/6 promotes replication fork stability and facilitates recombination-dependent repair when the BRC-1/BRD-1 complex initiates homologous recombination at stalled replication forks. (uni-koeln.de)
  • Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
  • Towards modulating the gut microbiota to enhance the efficacy of immune-checkpoint inhibitors. (cdc.gov)
  • This includes whether and how the immune system reacts to emerging tumours, whether antitumour immune responses are reactivated during treatment with immune-checkpoint inhibitors (ICIs), and whether unintended destructive immune pathologies accompany such treatment. (cdc.gov)
  • Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. (nih.gov)
  • Here, we show that Claspin associates with several core replication fork proteins in Xenopus egg extracts. (caltech.edu)
  • We identified a replication fork-interacting domain on Claspin that associates with the replication fork proteins and is required for Claspin association with chromatin. (caltech.edu)
  • We are interested in understanding at the molecular level how recombination occurs and what roles are played by the many proteins involved in DNA recombination, repair and replication. (brandeis.edu)
  • We are interested in determining what are the specific biochemical roles played by the many proteins implicated in DNA recombination, repair and replication. (brandeis.edu)
  • We have identified the proteins necessary to carry out the initial steps in strand invasion and the beginning of new DNA synthesis, which is significantly different from the normal process of replication. (brandeis.edu)
  • The structural maintenance of chromosomes (SMC) proteins form distinct complexes that maintain genome stability during chromosome segregation, homologous recombination, and DNA replication. (uni-koeln.de)
  • and the contribution of chromatin-modifying proteins to replication and repair. (usc.edu)
  • Knocking out SOG1 in the fast weel background restores replication stress sensitivity, demonstrating that SOG1 is an important secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint. (muni.cz)
  • I've found a number of articles on the web for setting up streaming replication in PostgreSQL, but none of them seemed to actually put everything together that I needed, and none of them seemed to use the new pg_basebackup in PostgreSQL 9.1 and later. (rassoc.com)
  • Chk1 facilitates the arrest of cell cycle progression and the inhibition of replication origin firing. (caltech.edu)
  • Claspin has two broadly defined roles, one to mediate Chk1 activation and the other as a component of the replication fork. (caltech.edu)
  • Thus, the localization of Claspin to the replication fork is not required for mediation of Chk1 activation but it does potentiate this process. (caltech.edu)
  • Accumulation of Drf1 on chromatin in the presence of replication blocks is dependent upon ATR and Claspin but not Chk1. (caltech.edu)
  • 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)
  • 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)
  • Germ cells of smc-5-defective animals show reduced proliferation, sensitivity to perturbed replication, chromatin bridge formation, and accumulation of RAD-51 foci that indicate the activation of homologous recombination at DNA double-strand breaks. (uni-koeln.de)
  • Our data suggest that BRC-1/BRD-1 can both promote and antagonize genome stability depending on whether homologous recombination is initiated during DNA double-strand break repair or during replication stalling. (uni-koeln.de)
  • In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. (nih.gov)
  • DNA replication is initiated by the S-CDK and DDK kinases which mediate the unwinding of the replication fork. (caltech.edu)
  • We have found that a DNA replication checkpoint dependent on the ATM homolog MEC1 operates in wild-type cells during meiosis and can be invoked in response to inhibition of DNA synthesis. (ox.ac.uk)
  • 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)
  • Despite this defect, the mutant cells progress into the meiotic program and undergo lethal segregation of unreplicated DNA suggesting that they fail to activate a checkpoint that restrains meiotic M phase until DNA replication is complete. (ox.ac.uk)
  • Otherwise, if restart_lsn of a replication slot falls behind the current LSN by more than the given size, the standby using the slot may no longer be able to continue replication due to removal of required WAL files. (postgresql.org)
  • In the distributed computing environment, checkpointing is a technique that helps tolerate failures that otherwise would force long-running application to restart from the beginning. (wikipedia.org)
  • One of the original and now most common means of application checkpointing was a "save state" feature in interactive applications, in which the user of the application could save the state of all variables and other data to a storage medium at the time they were using it and either continue working, or exit the application and at a later time, restart the application and restore the saved state. (wikipedia.org)
  • Thus the "checkpoint/restart" capability was born, in which after a number of transactions had been processed, a "snapshot" or "checkpoint" of the state of the application could be taken. (wikipedia.org)
  • Thus the number of records processed for each checkpoint might range from 25 to 200, depending on cost factors, the relative complexity of the application and the resources needed to successfully restart the application. (wikipedia.org)
  • FTI is a library that aims to provide computational scientists with an easy way to perform checkpoint/restart in a scalable fashion. (wikipedia.org)
  • The tradeoff is that if this option is specified, that a failed replication must restart without a checkpoint. (apache.org)
  • In addition cells have evolved a damage-sensing checkpoint system whereby the cells delay entry into mitosis until the break has been repaired. (brandeis.edu)
  • A vertebrate gene, ticrr, is an essential checkpoint and replication regulator. (ouhsc.edu)
  • Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. (nih.gov)
  • The Forsburg lab uses a mixture of classical genetics, molecular biology, and state-of-the-art microscopy to investigate how defects in replication contribute to genome instability during normal cell growth and during the differentiation process of meiosis. (usc.edu)
  • This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. (avivasysbio.com)
  • Results HIV-rtTA does not induce CD4+ T-cell depletion in blood despite active replication in the presence of dox BRG-HIS mice (12-15 weeks old) were infected intraperitoneally with 5×104 TCID50 of the HIV-rtTA variant (gene of the HIV-1 … Fig. 2. (biospraysehatalami.com)
  • HIV-rtTA does not induce CD4+ T-cell depletion in blood despite active replication in the presence of dox. (biospraysehatalami.com)
  • These effects resulted in significant accumulation of unreplicated single-stranded DNA and increased cell death, indicative of replication catastrophe. (nature.com)
  • These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
  • Preclinical models predict that blockade of the coinhibitory molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on lymphocytes results in the release of a cell cycle inhibitory checkpoint, allowing lymphocyte proliferation, tumor targeting, and regression. (snmjournals.org)
  • We tested the role of whole-body molecular imaging in patients with advanced melanoma receiving the CTLA4-blocking antibody tremelimumab, allowing the analysis of changes in glucose metabolism using the PET probe 18 F-FDG and cell replication with the PET probe 3′-deoxy-3′- 18 F-fluorothymidine ( 18 F-FLT). (snmjournals.org)
  • RAD9A is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair in response to DNA damage. (avivasysbio.com)
  • These settings control the behavior of the built-in streaming replication feature (see Section 27.2.5 ), and the built-in logical replication feature (see Chapter 31 ). (postgresql.org)
  • For more details about logical replication configuration settings refer to Section 31.10 . (postgresql.org)
  • Forsburg takes a holistic approach to studying how DNA replication stress contributes to genome stability. (usc.edu)
  • It forms a checkpoint protein complex with RAD1 and HUS1. (avivasysbio.com)
  • There are two main approaches for checkpointing in the distributed computing systems: coordinated checkpointing and uncoordinated checkpointing. (wikipedia.org)
  • We have shown that there are differences between this repair-induced replication fork and the normal replication process, but there is much more work to do. (brandeis.edu)
  • This high-density, quantitative genetic interaction map focused on various aspects of chromosome function, including transcription regulation and DNA repair/replication. (thebiogrid.org)
  • This section discusses known problems or issues when using replication with NDB Cluster. (mysql.com)
  • For this reason, to guarantee high availability, it is extremely important to maintain a backup replication channel, to monitor the primary channel, and to fail over to the secondary replication channel when necessary to keep the replica cluster synchronized with the source. (mysql.com)
  • See Section 23.7.8, "Implementing Failover with NDB Cluster Replication" , for more information about what to do in such circumstances. (mysql.com)
  • Because NDB Cluster is not designed on its own to monitor replication status or provide failover, if high availability is a requirement for the replica server or cluster, then you must set up multiple replication lines, monitor the source mysqld on the primary replication line, and be prepared fail over to a secondary line if and as necessary. (mysql.com)
  • For information about implementing this type of setup, see Section 23.7.7, "Using Two Replication Channels for NDB Cluster Replication" , and Section 23.7.8, "Implementing Failover with NDB Cluster Replication" . (mysql.com)
  • NDB Cluster Replication supports circular replication, as shown in the next example. (mysql.com)
  • The replication setup involves three NDB Clusters numbered 1, 2, and 3, in which Cluster 1 acts as the replication source for Cluster 2, Cluster 2 acts as the source for Cluster 3, and Cluster 3 acts as the source for Cluster 1, thus completing the circle. (mysql.com)
  • In contrast, the DNA damage accumulation and sensitivity of smc-5 mutant strains to replication impediments are suppressed by mutations in the C. elegans BRCA1/BARD1 homologs, brc-1 and brd-1. (uni-koeln.de)
  • Drf1 forms a stable, active complex with Cdc7, even after replication arrest in egg extracts. (caltech.edu)
  • We demonstrate that lack of FAS1 activity results in the activation of an ATAXIA TELANGIECTASIA MUTATED (ATM)- and SUPPRESSOR OF GAMMA-RESPONSE 1 (SOG1)-mediated G2/M-arrest that renders the ATR and WEE1 checkpoint regulators redundant. (muni.cz)
  • But how exactly this DNA doubling takes place was at first a mystery, and scientists began to propose several possible mechanisms, or "models" of DNA replication? (visionlearning.com)
  • These parameters can be set on any server that is to send replication data to one or more standby servers. (postgresql.org)
  • Rather, it will read the latest state ("the checkpoint") from the stable storage and execute from that. (wikipedia.org)
  • The test does an unclean shutdown on the only node in the replica set, which means that it can fail to get the proper fcv document into the stable checkpoint before it shuts down, which will result in an error during startup. (mongodb.org)
  • After you have concluded your testing, discard the test virtual machine by choosing Stop Test Failover under the Replication option or simply delete the test virtual machine directly . (experts-exchange.com)
  • I only wanted to delete the failover test created VM, but the checkpoint was on the actual replica VM. (experts-exchange.com)
  • For streaming replication , servers will be either a primary or a standby server. (postgresql.org)
  • When cascading replication (see Section 27.2.7 ) is used, standby servers can also be senders, as well as receivers. (postgresql.org)
  • directory, in case a standby server needs to fetch them for streaming replication. (postgresql.org)
  • megabytes, the sending server might remove a WAL segment still needed by the standby, in which case the replication connection will be terminated. (postgresql.org)
  • is zero (the default), the system doesn't keep any extra segments for standby purposes, so the number of old WAL segments available to standby servers is a function of the location of the previous checkpoint and status of WAL archiving. (postgresql.org)
  • You forgot to set up replication on the standby. (stackexchange.com)
  • We report here that cells undergoing meiotic development also require Clb dependent CDK activity for DNA replication. (ox.ac.uk)
  • This is the process we have studied most intensively, but we are also interested in an alternative process known as break-induced replication (BIR), where only one end of a chromosome break locates a template sequence and assembles a complete replication fork and can copy sequences to the end of a chromosome, producing a nonreciprocal translocation. (brandeis.edu)
  • A novel genetic approach for the control of virus replication was used for the design of a conditionally replicating human immunodeficiency virus (HIV) variant HIV-rtTA. (biospraysehatalami.com)
  • Therefore, we conclude that DDK regulates a largely checkpoint-independent role of Claspin function. (caltech.edu)
  • In the uncoordinated checkpointing, each process checkpoints its own state independently. (wikipedia.org)
  • Some envisioned replication as proceeding in short stretches, while others imagined a continuous process much like a zipper. (visionlearning.com)
  • are not part of the replication process. (stackexchange.com)
  • The approach also provides a framework for understanding and designing replication management protocols. (wikipedia.org)