Dna damage checkpoint in schizosaccharomyces. Medical search. Frequent questions

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)
This protein and ATM share similarity with Schizosaccharomyces pombe rad3, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. (utsouthwestern.edu)
In the fission yeast Schizosaccharomyces pombe, deletion of pot1+ results in rapid telomere loss, and the resulting survivors have circular chromosomes. (bvsalud.org)
Professor Forsburg studies how chromosome duplication and maintenance contributes to overall genome stability using a simple model genetic system, the fission yeast Schizosaccharomyces pombe . (usc.edu)
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)
An epistasis map (E-MAP) was constructed in the fission yeast, Schizosaccharomyces pombe, by systematically measuring the phenotypes associated with pairs of mutations. (thebiogrid.org)
To understand better the contribution of hypermutagenesis to tumour development, we have modelled the most recurrent POLE-EDM (POLE-P286R) in Schizosaccharomyces pombe. (ox.ac.uk)
This review is concerned with repair and tolerance of UV damage in the fission yeast, Schizosaccharomyces pombe and with the differences between Sch. (infona.pl)
Abstract An artificially created non-tandem heteroallelic duplication was constructed to assay mitotic intrachromosomal recombination in Schizosaccharomyces pombe. (infona.pl)
Abstract Caffeine potentiates the lethal effects of ultraviolet and ionising radiation on wild-type Schizosaccharomyces pombe cells. (infona.pl)
In previous studies this was attributed to the inhibition by caffeine of a novel DNA repair pathway in S. pombe that was absent in the budding yeast Saccharomyces cerevisiae. (infona.pl)
Schizosaccharomyces pombe strains containing direct repeats of ade6 heteroalleles separated by a functionalura4 + gene, and a DNA site for induction of a double-strand break (DSB), have been used to analyze pathways of spontaneous and DSB-induced intrachromosomal mitotic recombination. (infona.pl)
Caspari T, Dahlen M, Kanter-Smoler G, Lindsay HD, Hofmann K, Papadimitriou K, Sunnerhagen P and Carr AM, 2000 , Characterization of Schizosaccharomyces pombe Hus1: a PCNA-related protein that associates with Rad1 and Rad9. (bangor.ac.uk)
Human Rad 9 ( hRad9 ) was originally identified as a structural homologue of yeast schizosaccharomyces pombe rad 9 , which can partially rescue the sensitivity of rad 9 null yeast to hydroxyurea, radiation damage and the associated checkpoint defects [ 1 ]. (biomedcentral.com)
The protein products of several rad checkpoint genes of Schizosaccharomyces pombe (rad1 + , rad3 + , rad9 + , rad17 + , rad26 + , and hus1 + ) play crucial roles in sensing changes in DNA structure, and several function in the maintenance of telomeres. (elsevierpure.com)
abstract = "The protein products of several rad checkpoint genes of Schizosaccharomyces pombe (rad1+, rad3+, rad9+, rad17+, rad26+, and hus1+) play crucial roles in sensing changes in DNA structure, and several function in the maintenance of telomeres. (elsevierpure.com)

Pot1 binds to single-stranded telomere DNA and is conserved from fission yeast to humans. (bvsalud.org)
Collectively, we propose that fission yeast Stn1 primarily safeguards the semi-conservative DNA replication at telomeres and subtelomeres. (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)

Rad3 also phosphorylates a number of other proteins whose absence abolishes checkpoint DNA repair, including rad1, rad9, hus1 and rad17. (wikipedia.org)
It has been hypothesized that rad9, hus1 and rad17 are similar to proteins involved in forming the clamp that increases the processivity of DNA polymerase during DNA replication. (wikipedia.org)
In agreement with this idea, rad17 is similar to proteins involved in loading the clamp onto DNA. (wikipedia.org)
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)
The S. cerevisiae checkpoint protein Rad17, the orthologue of human Rad1, forms a homocomplex in response to treatment with DNA damaging agents, and the complex is required for yeast survival after exposure to genotoxic agents [ 12 ]. (biomedcentral.com)
This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (utsouthwestern.edu)
The 9-1-1 complex is a heterotrimeric ring-shaped structure that is loaded onto DNA by the Rad17-RFC complex. (reactome.org)
During ATR signaling in response to DNA damage, Rad17 forms a complex with 9-1-1 and loads onto stalled replication forks [ 4 - 9 ]. (biomedcentral.com)

The main rad3 effector is the kinase Chk1, which is required for the G2-M arrest in response to DNA-damaging agents. (wikipedia.org)
In addition, we investigated several cell cycle-related proteins and found that co-knockdown of hTopBP1 and hMYH significantly diminished cell cycle arrest due to compromised checkpoint kinase 1 (Chk1) activation. (biomedcentral.com)
It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which unattached kinetochores prevent anaphase onset. (rupress.org)
Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal. (rupress.org)

Loss of function of oncogenes, tumor suppressor genes and DNA damage processing genes has been implicated in the development of many types of cancer, but for the vast majority of cases, there is no link to specific germ line mutations. (aacrjournals.org)
Because the effect of haploinsufficiency for one protein is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes, critical for pathways that control DNA damage signaling, repair or apoptosis. (aacrjournals.org)
Liu C, Powell KA, Mundt K, Wu L, Carr AM, Caspari T., 2003 , Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms Genes Dev. (bangor.ac.uk)

It is likely that increased Rad9 expression is needed for proliferation of tumor cells by mechanisms such as getting beyond (tolerating) oncogene-induced replicative stress and enhancing DNA repair capability. (biomedcentral.com)
To address this issue, primary mouse cells, haploinsufficient for one or two proteins, ATM and RAD9, related to the cellular response to DNA damage were examined. (aacrjournals.org)
The results show that cells having low levels of both ATM and RAD9 proteins are more sensitive to transformation by radiation, have different DNA double-strand break repair dynamics and are less apoptotic when compared with wild-type controls or those cells haploinsufficient for only one of these proteins. (aacrjournals.org)
Our conclusions are that under stress conditions, the efficiency and capacity for DNA repair mediated by the ATM/RAD9 cell signaling network depend on the abundance of both proteins and that, in general, DNA repair network efficiencies are genotype-dependent and can vary within a specific range. (aacrjournals.org)
Moreover, we observed that hMYH was essential for the accumulation of hTopBP1 on damaged DNA, where hTopBP1 interacts with hRad9, a component of the Rad9-Hus1-Rad1 complex. (biomedcentral.com)
This telomere instability correlated with enhanced S- and G 2 -phase- specific cell killing, delayed kinetics of γ-H2AX focus appearance and disappearance, and reduced chromosomal repair after ionizing radiation (IR) exposure, suggesting that Rad9 plays a role in cell cycle phase-specific DNA damage repair. (elsevierpure.com)

This high-density, quantitative genetic interaction map focused on various aspects of chromosome function, including transcription regulation and DNA repair/replication. (thebiogrid.org)
TP53 is a checkpoint molecule that maintains genomic stability, prevents cell mitosis and induces apoptosis following abnormal chromosome segregation or chemical damage to DNA sequences [ 9 , 10 ]. (biomedcentral.com)
DSBs not only ensue from normal cellular metabolism, in the form of reactive oxygen species that can oxidize DNA bases [ 1 , 2 ], but can also be generated during physiological processes like chromosome replication, meiotic recombination and DNA replication transcription collision [ 3 - 7 ]. (springeropen.com)
Eukaryotic DNA replication initiates at multiple origin sites along each chromosome and terminates when replication forks (RFs) from adjacent origins converge. (elifesciences.org)

Early signaling proteins in the checkpoint pathway are members of a family of phosphatidylinositol 3-kinases, rad3 in yeast and ATR in vertebrates, that are believed to localize to sites of DNA damage. (wikipedia.org)
Rad3 phosphorylates rad26 which is required to initiate, but not maintain the checkpoint. (wikipedia.org)
This supports a model where phosphorylation by rad3 causes recruitment of these proteins to sites of DNA damage where they mediate the activity of DNA polymerases involved in DNA repair. (wikipedia.org)
In addition, S phase is aberrant and RPA foci are elevated, suggestive of ssDNA or DNA damage, and the pol2-P287R mutation is synthetically lethal with rad3 inactivation, indicative of checkpoint activation. (ox.ac.uk)
The ataxia telangiectasia and Rad3-related protein (ATR) signaling cascade is an important pathway involved in the checkpoint control mechanism [ 3 ]. (biomedcentral.com)

It forms a checkpoint protein complex with RAD1 and HUS1. (avivasysbio.com)
Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)

Proteins that localize to sites of DNA damage in the G2 phase initiate a signaling cascade that regulates important components of the pathway, as described above, therefore controlling mitotic entry via CyclinB-Cdc2 activity. (wikipedia.org)
Inefficient repair of DNA damaged by ionizing radiation or chemical agents in these mutants revealed proteins essential in this pathway. (wikipedia.org)
Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an important role in DNA replication and the DNA damage checkpoint pathway. (biomedcentral.com)
Thus, hTopBP1 constitutes an important part of the ATR signaling pathway and acts as a molecular bridge that associates the independently recruited 9-1-1 and ATR-ATRIP complexes, thereby leading to checkpoint activation [ 4 ]. (biomedcentral.com)
A second NHEJ concomitant pathway often referred to as alternative-NHEJ (Alt-NHEJ), also known as Microhomology-mediated end joining (MMEJ), is another well-studied pathway for repairing DSBs in DNA [ 16 ]. (springeropen.com)
Chemotherapeutic agents that damage DNA activate the p53 pathway and can initiate cancer cell death [ 1 , 2 ]. (oncotarget.com)

In the last several years, heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways was shown to play a role in genomic instability and carcinogenesis after DNA damage is induced. (aacrjournals.org)
In the last few years, mounting evidence suggests that heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways plays a role in genomic instability and carcinogenesis. (aacrjournals.org)
Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. (biomedcentral.com)
Genomic instability is defined as an increased rate of DNA alterations [ 8 ]. (biomedcentral.com)
The loss of proper response to DNA damage leads to genomic instability such as gene mutations, incomplete replication and the loss or gain of chromosomes to future generations. (biomedcentral.com)
Problems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. (elifesciences.org)

The human mutY homolog (hMYH) is a base excision repair DNA glycosylase that excises adenines or 2-hydroxyadenines that are mispaired with guanine or 7,8-dihydro-8-oxoguanine (8-oxoG). (biomedcentral.com)

Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. (biomedcentral.com)
We have been fascinated by the process of yeast mating-type gene switching, in which cells replace about 700 bp of Ya or Y-specific DNA sequences at the MAT locus by recombining with one of two donor loci, called HMLDescription: image3 and HMRa. (brandeis.edu)
hRad9 is a cell cycle checkpoint gene that is up-regulated in breast cancer. (biomedcentral.com)

Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth. (biomedcentral.com)

Cells with a defective G2-M checkpoint will undergo apoptosis or death after cell division if they enter the M phase before repairing their DNA. (wikipedia.org)
Keratinocytes isolated from Mrad1 +/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1 +/+ control cells. (biomedcentral.com)
However, in established cancer cells, such DNA repair system may prevent further DNA damage in their progeny and decrease in apoptosis resulting in enhancement of tumor growth. (biomedcentral.com)
Thus, in addition to its checkpoint control function, hRad9 may play a role in regulating apoptosis. (biomedcentral.com)

Upon loading, the 9-1-1 complex can recruit Chk1 onto sites of replication fork uncoupling or DNA damage. (reactome.org)
hTopBP1 and hMYH were involved in ATR-mediated Chk1 activation, moreover, both of them were associated with ATR and hRad9 which known as checkpoint-involved proteins. (biomedcentral.com)
Our results suggested that hMYH is necessary for the accumulation of hTopBP1 to DNA damage lesion to induce the association of hTopBP1 with 9-1-1 and that the interaction between hMYH and hTopBP1 is essential for Chk1 activation. (biomedcentral.com)

The loss of chromosomal DNA happened without gradual telomere shortening, and extended to 30 kb from the ends of chromosomes. (nih.gov)
The genetic information in eukaryotic cells is stored in linear DNA molecules known as chromosomes [ 1 ]. (actanaturae.ru)

Normally, structural damage of DNA by endogenous and environmental agents is followed by replication checkpoint arrest at the G2/M transition in order to allow for repair before proceeding in the cell cycle. (biomedcentral.com)
Structure-guided point mutations in either CAPN7 MIT domain disrupted IST1 binding in vitro and in cells, and depletion/rescue experiments showed that the CAPN7-IST1 interaction is required for: 1) CAPN7 recruitment to midbodies, 2) efficient abscission, and 3) NoCut checkpoint arrest. (elifesciences.org)

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)
We find that MHF stimulates DNA binding and replication fork remodeling by FANCM. (infona.pl)
Iyer DR, Rhind N. Replication fork slowing and stalling are distinct, checkpoint-independent consequences of replicating damaged DNA. (umassmed.edu)

Both homologous recombination, in which the ends of the broken DNA seek out intact templates with the same sequence, and nonhomologous end-joining pathways are found in Saccharomyces as they are in humans. (brandeis.edu)

One of the oxidative DNA lesions frequently generated upon exposure of cells to reactive oxygen species (ROS) is 7,8-dihydro-8-oxoguanine (8-oxoG) [ 13 ]. (biomedcentral.com)

The two most commonly used pathways to repair DSBs in higher eukaryotes include non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ is considered to be error-prone, intrinsically mutagenic quick fix remedy to seal together the broken DNA ends and restart replication. (springeropen.com)
DNA double strand break repair (DSBR) pathways are generally classified based on whether sequence homology is used to join the broken DNA ends. (springeropen.com)

Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)

hRad9 is a nuclear protein that interacts with hRad1 and hHus1 to form a hetero-trimeric complex (the 9-1-1 complex) which is then loaded onto DNA [ 9 ]. (biomedcentral.com)
The C-terminal domain of hRad9 contains phosphorylation sites and hyperphosphorylation of hRad9 occurs in response to DNA damage [ 10 ]. (biomedcentral.com)

We find that there is a 1000-fold increase in mutation rate and that about half the mutations have a distinctive "signature" suggesting that the DNA polymerase frequently dissociates and re-anneals with its template. (brandeis.edu)
Somatic and germline mutations in the proofreading domain of the replicative DNA polymerase ε (POLE-exonuclease domain mutations, POLE-EDMs) are frequently found in colorectal and endometrial cancers and, occasionally, in other tumours. (ox.ac.uk)

The defining biochemical feature of this checkpoint is the activation of M-phase cyclin-CDK complexes, which phosphorylate proteins that promote spindle assembly and bring the cell to metaphase. (wikipedia.org)
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)

The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms that ensures that cells don't initiate mitosis until damaged or incompletely replicated DNA is sufficiently repaired. (wikipedia.org)
The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at different checkpoints of the cell cycle. (wikipedia.org)
Negative regulation of CyclinB-Cdc2 activity results in a delay in mitotic entry, which is important for cells to repair any DNA damage that may have accumulated after S phase and necessary before cell division can continue. (wikipedia.org)
DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. (biomedcentral.com)
It is believed that this complex is important for the function of these three proteins in DNA repair as well as activation of cell cycle checkpoints. (biomedcentral.com)
Ovarian cancer cell DNA ploidy was determined using Feulgen-stained smears or flow cytometry. (biomedcentral.com)
Therefore, we suggest that the interaction between hMYH and hTopBP1 is crucial for activation of the ATR-mediated cell cycle checkpoint. (biomedcentral.com)
Activation of ATR phosphorylates a number of downstream proteins that coordinate the cell cycle checkpoint. (biomedcentral.com)
Shortening of the 5'-terminus of the daughter strand, caused by the removal of the terminal RNA-primer and the subsequent incomplete replication of linear DNA molecules, is observed during the genome replication occurring upon cell fission. (actanaturae.ru)

RDR can initiate from a collapsed fork where the DNA is either broken or remains intact. (elifesciences.org)

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)
Human DNA topoisomerase II-binding protein 1 (TopBP1) and its orthologs play important roles in DNA replication and checkpoint control [ 1 ]. (biomedcentral.com)
FANCM remodels branched DNA structures and plays essential roles in the cellular response to DNA replication stress. (infona.pl)

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

Another conclusion from most of the cases is that animals or cells haploinsufficient for the specified proteins have higher transformation rates after DNA damage is induced, but when their DNA is not significantly damaged by exogenous sources, tumor development rates are the same as for their wild-type counterparts. (aacrjournals.org)

Proteins that function in the G2-M checkpoint were originally identified in yeast screens that looked for mutants which show enhanced sensitivity to radiation, termed "rad" mutants. (wikipedia.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)

Under cellular stress conditions, such as DNA damage, wild-type p53 becomes activated and stabilized [ 5 , 6 ]. (oncotarget.com)

In the case of unreplicated DNA, the cyclin concentration threshold for Cdc2 activation is further increased. (wikipedia.org)
We found transient and modest single-stranded G-strand exposure, but did not find any evidence of checkpoint activation in stn1-1 at the restrictive temperature. (nih.gov)
Presumably the C-terminal domain is essential for transport of the 9-1-1 complex from the cytoplasm into the nucleus, for activation of the G2 checkpoint signalling cascade [ 12 ]. (biomedcentral.com)

These filaments also bind and recruit cofactors whose activities help execute abscission and/or delay abscission timing in response to mitotic errors via the NoCut/Abscission checkpoint. (elifesciences.org)

It is a regulatory molecule and a component of DNA, RNA, cofactors nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD) and signaling molecules (cAMP). (sigmaaldrich.com)

Here, we show that FANCM forms a conserved DNA-remodeling complex with a histone-fold heterodimer, MHF. (infona.pl)
During NHEJ, once a DSB is formed the broken ends are bound by Ku proteins (ku70 and ku80), which form a heterodimer and insulate the DNA ends from nucleolytic erosion [ 11 , 12 ]. (springeropen.com)

We have shown that the invasion of DNA strands into a donor template region requires the action of the chromatin remodeling protein Rad54 that enables the recombination machinery to gain access to "closed" regions of DNA. (brandeis.edu)
Recombination based mechanisms are crucial for both the repair and tolerance of DNA damage that vexes both strands of the double helix [ 9 ]. (springeropen.com)

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