Damage repair damage checkpoint pathway. Medical search. Frequent questions

The main rad3 effector is the kinase Chk1, which is required for the G2-M arrest in response to DNA-damaging agents. (wikipedia.org)
Surprisingly, we found that expression of ATM, a kinase that is recruited and activated by DNA double breaks as part of the DNA damage checkpoint, mimicked and/or mediated changes in TOP2 expression in these cells. (braintumour.ca)
In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)
NIMA (never-in-mitosis gene A)-related kinase 1 (Nek1) is shown to impact on different cellular pathways such as DNA repair, checkpoint activation, and apoptosis. (uni-frankfurt.de)
ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage. (elsevierpure.com)
Together, our findings identify ATR as the kinase responsible for activating the FA pathway of DNA repair. (elsevierpure.com)
Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
An inhibitor of ataxia telangiectasia and rad3-related (ATR) kinase, a DNA damage response kinase, with potential antineoplastic activity. (cancertreatmentsresearch.com)
Upon administration, berzosertib selectively binds to and inhibits ATR kinase activity and prevents ATR-mediated signaling in the ATR-checkpoint kinase 1 (Chk1) signaling pathway. (cancertreatmentsresearch.com)
Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.com)
8 , 9 The protein is a member of a novel family of large proteins, which show sequence homology to the catalytic domain of phosphatidylinositol 3 kinase, 3 and are implicated in cell cycle regulation, signal transduction, and the response to DNA damage. (bmj.com)
The mitotic kinase monopolar spindle 1 (Mps1) is a key regulator of the Spindle assembly checkpoint, which ensures the correct chromosome segregation. (lu.se)

ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
All of these defects are associated with impaired activation of the ATR/CHK1 pathway. (nature.com)
Targeting ATR/CHK1 cell cycle checkpoint is a new approach in the post-PARPi era. (nih.gov)

During RT, alterations in signaling pathways result in changes in the local immune microenvironment. (nature.com)
Alterations in components of the p53 pathway, such as amplification of the Mdm2 gene, which encodes a p53 inhibitor, also contribute to tumorigenesis. (mdanderson.org)
Linkage with immunotherapy and PARP inhibitors was identified in 44% of glioblastoma patients because of alterations in DNA-damage repair genes. (businesswire.com)
These alterations can take the form of epigenetic modifications, point mutations, translocations, amplifications or deletions and modify gene functions in ways that deregulate cellular signalling pathways leading to the cancer phenotype. (bmj.com)
9 The exact number and nature of genetic alterations and deregulated signalling pathways required for tumorigenesis remains an issue of debate, 10 although it is now clear that central nervous system (CNS) carcinogenesis requires multiple disruptions to the normal cellular circuitry. (bmj.com)
Genotoxic damage causes robust alterations to pathways associated with B cell activation and increased proliferation, suggesting that genotoxic damage initiates not only the normal B cell maturation processes but also mimics activated B cell response to antigenic agents. (biomedcentral.com)
Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. (bmbreports.org)
DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)
Furthermore, poorer prognosis in cancer patients who display a glycolytic phenotype characterized by metabolic alterations, such as obesity and diabetes, is now well established, providing another link between metabolic pathways and cancer progression. (springer.com)
Metabolomics analysis showed significant alterations in urinary metabolites (i.e., glucoses, lipids and amino acids) after PM2.5 exposure, simultaneously accompanied by activation of the cAMP signaling pathway. (bvsalud.org)
The main idea is that posttranslational modifications, including those of the ubiquitin family, lead to alterations in interactions between proteins that perform the necessary repair steps. (umcg.nl)
In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
Phase II Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations. (cdc.gov)

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)
If cells containing damaged DNA were to divide, the errors would be transmitted to daughter cells, generating genomic instability and resulting in tumorigenesis or apoptosis . (tocris.com)
Stably transduced doxycycline (Dox)-inducible Nek1 shRNA HeLa cervix and siRNA-transfected HCT-15 colorectal carcinoma cells were irradiated in vitro and 3D clonogenic radiation survival, residual DNA damage, cell cycle distribution, and apoptosis were analyzed. (uni-frankfurt.de)
Activated p53 induces programmed cell death (apoptosis) or senescence as a last attempt to avoid possible malignant transformation when the damage is too severe and beyond repair. (medium.com)
Therefore, there are multiple conserved pathways within cells that respond to such errors by recruiting DNA repair processes or initiating apoptosis. (medium.com)
Caspase-2 is most well-known for initiating the intrinsic apoptosis pathway [1] and as a tumor suppressor [2]. (nature.com)
This indicates a role distinct from caspase-2's reported role in inducing apoptosis to remove damaged or aneuploid cells [7][8]. (nature.com)
While other groups have demonstrated non-apoptotic roles for caspase-2 in DNA repair, cell cycle arrest [2], this is the first demonstration that these roles are regulated by a distinct pathway to apoptosis. (nature.com)
This prevents DNA damage checkpoint activation, disrupts DNA damage repair, and induces tumor cell apoptosis. (cancertreatmentsresearch.com)
The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)

Selective up-regulation of expression of a subset of genes, including those involved in S-phase checkpoints and the CYCB1;1 gene at the G₂-to-M transition, was observed in Atasf1ab. (nih.gov)
Furthermore, the Atasf1ab-triggered replication fork stalling constitutively activates the DNA damage checkpoint and repair genes, including ATM, ATR, PARP1 and PARP2 as well as several genes of the homologous recombination (HR) pathway but not genes of the non-homologous end joining (NHEJ) pathway. (nih.gov)
In spite of the activation of repair genes, an increased level of DNA damage was detected in Atasf1ab, suggesting that defects in the mutant largely exceed the available capacity of the repair machinery. (nih.gov)
We found that the more thermally tolerant population had greater plasticity of gene expression and had significantly more downregulated genes, which may provide more energy to repair damage associated with thermal stress and to maintain basic functions at these extreme temperatures. (frontiersin.org)
We list the DNA repair genes and related E3 ligases. (bmbreports.org)
The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
Loss of functional DNA repair genes is a key feature of base pair mutations found in hereditary cancers. (medium.com)
this protein prevents efficient repair of DNA damage, leading to the accumulation of mutations in other genes. (diff.org)
For example, in the hereditary cancer syndromes familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, mutations have been discovered in the APC gene and DNA mismatch repair genes. (medscape.com)
The main role of p53 as a tumor suppressor relies on its transcriptional activity to regulate target genes in a variety of biological pathways (Sullivan et al. (villajoyosacf.info)

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)
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)
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)
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)
Inefficient repair of DNA damaged by ionizing radiation or chemical agents in these mutants revealed proteins essential in this pathway. (wikipedia.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 also phosphorylates a number of other proteins whose absence abolishes checkpoint DNA repair, including rad1, rad9, hus1 and rad17. (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)
Studies in yeast and animals indicate that ASF1 proteins play important roles in various chromatin-based processes, including gene transcription, DNA replication and repair. (nih.gov)
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)
Ageing leads to a gradual dysfunction of the proteostasis network and thus to proteome instability due to accumulation of damaged and/or misfolded proteins [ 2 ]. (hindawi.com)
The mitochondria have their own chaperones and proteolytic enzymes that remove damaged or unfolded proteins [ 18 - 20 ]. (hindawi.com)
Whereas the different DNA repair pathways and the proteins they involve are know pretty well described, how they are regulated relative to each other in time and space remains to be deciphered. (cea.fr)
It seems now clear that posttranslational modification of both DNA repair and checkpoint proteins is of importance for the regulation of their activities but how these modifications are regulated and how they affect the activity of the proteins only begins to be described. (cea.fr)
The duplication of chromosomes and the regulation of their replication and repair requires dozens of proteins acting together to maintain the duplex DNA genome. (rockefeller.edu)
This family consists of the repair proteins Rad1, Rec1 and Rad17. (embl.de)
As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. (bmbreports.org)
The mechanisms of DNA repair is closely coupled with the DNA damage response (DDR), which involves the recruitment and localization within distinct nuclear foci of DNA damage sensors, mediators, transducers and effector proteins ( Polo and Jackson 2011 ). (medium.com)
The histones and non-histone proteins of chromatin compact the DNA and govern its accessibility to enzymes during transcription, replication, repair and recombination. (biomedcentral.com)
In this review, we describe the effects of MDM2 on genomic instability, the role of MDM2 in p53 release and binding of DNA repair proteins to inhibit repair, and the regulatory network of MDM2, including its transcriptional modifications, protein stability, and localization. (villajoyosacf.info)
Among the two major double-strand break repair pathways, p53 interacts with both non-homologous end-joining (NHEJ) and homologous recombination (HR) proteins at the RAD51 promoter to regulate its expression (Williams and Schumacher, 2016). (villajoyosacf.info)
This reaction, referred to as the DNA-damage response (DDR), is typically initiated by proteins that recognize DNA lesions, and is followed by the recruitment and activation of proteins that trigger checkpoint signaling or directly perform the necessary repair steps. (umcg.nl)
For example, upon binding to DNA lesions Rad23b dissociates from XPC (two proteins involved in nucleotide excision repair) in vivo 3 . (umcg.nl)
4 , 10 There is evidence to suggest that these proteins respond to DNA damage by phosphorylating one or more substrates, including p53, c-Abl, and replication protein A (RPA), to recruit proteins to regions of DNA repair and/or to activate radiation signal transduction pathways. (bmj.com)

Dr. Lozano is recognized as a pioneer in describing the p53 pathway, a recognized tumor suppressor gene associated with cancer. (mdanderson.org)
Lozano has been elected to the National Academy of Sciences (NAS) for her pioneering work in describing the p53 pathway, a recognized tumor suppressor gene associated with cancer. (mdanderson.org)
The new pembrolizumab approval covers adult and pediatric patients with any type of tumor that exhibits microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). (medpagetoday.com)
Tumor initiation, progression, and evolution are often rooted in the malfunctioning of the checkpoints securing genome integrity. (biomedcentral.com)
The tumor suppressor gene p53 regulates cell cycle arrest to allow time for DNA repair. (villajoyosacf.info)
The tumor suppressor p53 is recruited directly to sites of DNA damage in both a sequence-specific and non-specific manner to play a protective role in the DDR (Lee et al. (villajoyosacf.info)

This may suggest that caspase-2 activates a non-canonical replication checkpoint to facilitate DNA repair. (nature.com)

The limited changes in gene regulation suggest that individuals have reduced genome plasticity to tolerate thermal fluctuations and consequently may not have enough energy to repair damage and resume cellular homeostasis at extreme temperatures. (frontiersin.org)
The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. (thermofisher.com)
Double strand (ds) DNA breaks are a form of DNA damage that can be generated from both genotoxic exposures and physiologic processes, can disrupt cellular functions and can be lethal if not repaired properly. (biomedcentral.com)
DNA can be damaged in many different ways as a result of exogenous and endogenous forms of cellular stress. (umcg.nl)
DNA damage-induced posttranslational modifications are therefore a cellular way to assemble the DNA repair protein complexes required to counteract the genomic insults. (umcg.nl)
Dr. Maity obtained his Ph.D. in Cellular and Molecular Biology from the Life Science and Biotechnology department at Jadavpur University, India in 2017, where he studied the DNA damage repair protein WRN and autophagy. (nih.gov)

Here we compare transcriptional responses to physiological DNA breaks with responses to genotoxic DNA damage induced by ionizing radiation. (biomedcentral.com)
One such damage source is ionizing radiation (IR), which can be generated from both natural and man-made sources including radon gas and medical devices and procedures. (biomedcentral.com)
for example, ultraviolet light, ionizing radiation or DNA damaging chemicals are just some of the elements that create DNA replication breaks. (medium.com)

For a cell to progress through the cycle and replicate, it must pass through checkpoints between phases to ensure that DNA is replicated correctly and that chromosomes segregate. (tocris.com)
DSBs are first detected and signaled by the DNA damage checkpoint that triggers cell cycle arrest, providing time for the cell to repair damaged chromosomes before entering mitosis. (cea.fr)

Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
In contrast, while caspase-2-deficiency led to an increased proportion of S-phase cells and a progressive decrease in the proportion of G1-phase cells following treatment with arresting concentrations of the DNA damaging agent camptothecin and increased DNA damage following S-phase arrest, overexpression of Bcl-X L did not change the cell cycle profiles or the amount of DNA damage. (nature.com)
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)
Conversely, intact damage can lead to transcription and replication arrest, leading to cell death and senescence (Hoeijmakers, 2009). (villajoyosacf.info)
DNA damage usually induces the activation of DNA repair pathways and often a cell cycle arrest (a check point response). (umcg.nl)

In a Phase II study, MD Anderson researchers showed that a regimen of neoadjuvant and adjuvant treatment with checkpoint inhibitors nivolumab, a PD-1 inhibitor, and relatlimab, a LAG-3 inhibitor, was safe and effective in patients with resectable clinical stage III melanoma. (mdanderson.org)
Homologous recombination is a robust, broadly error-free mechanism of double-strand break repair, and deficiencies lead to PARP inhibitor sensitivity. (biomedcentral.com)

DNA damage, genetic instability, nucleotide excision repair, and the DNA damage checkpoint pathway) were altered in the 3D spheroid model. (usf.edu)
P53 deficiency results in reduced repair activity and decreased cell survival after UV-induced DNA damage, suggesting the involvement of p53 in nucleotide excision repair (NER) (Smith et al. (villajoyosacf.info)

Checkpoint control kinases is a term used to describe a group of enzymes that regulate progression of a cell through the cell cycle. (tocris.com)
Checkpoint control kinases function to halt the cell cycle at these critical points. (tocris.com)
Tocris offers the following scientific literature for Checkpoint Control Kinases to showcase our products. (tocris.com)
Once recruited to DSB, these complexes get activated and induce the phosphorylation of numerous targets including transducing kinases, which subsequently phosphorylate downstream effectors to delay cell cycle and promote DNA repair. (cea.fr)
Additionally, the checkpoint kinases modify the chromatin surrounding DNA damages through phosphorylation of the H2A histone (H2AX in mammals). (cea.fr)
Change in localisation depends on the checkpoint kinases Tel1ATM and Mec1ATR and has a positive effect on spontaneous recombination. (cea.fr)

We could confirm the increased polyploidy upon Mps1 inhibition in neuroblastoma cell lines and PDX model, leading to mitotic catastrophe activating the caspase-dependent mitochondrial apoptotic pathway. (lu.se)

Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)

Maintaining the genomic machinery is not a flawless process: DNA damage, genotoxic stresses, and defects in the repair pathways can all contribute to destabilizing the complex molecular networks keeping the genome intact. (biomedcentral.com)
I will be elaborating on the stages of DNA surveillance and repair and demonstrate how defects in the regulation of any of these mechanisms often results in genomic instability, which predisposes the cell to malignant transformation. (medium.com)
We show that caspase-2 protects cells from a range of S-phase-related defects, including delayed exit from S-phase, increased stalled replication forks, increased new replication origins, and decreased repair of S-phase-associated chromosomal aberrations [6]. (nature.com)
Defects in DNA damage repair can lead to genomic instability and cancer development. (villajoyosacf.info)
Approximately 40% of high-grade serous ovarian cancer (HGSOC) has defects in homologous recombination (HR) DNA double-strand break (DSB) repair (e.g. (nih.gov)
BARD1 germline variants induce haploinsufficiency and DNA repair defects in neuroblastoma. (cdc.gov)

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)
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)

The p53 protein is activated in response to DNA damage, serving as a checkpoint in the elimination or repair of cells with damaged DNA. (mdanderson.org)
Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
These results suggest genotoxic damage may induce a unique cancer-prone phenotype and processes mimicking activated B cell response to antigenic agents, as well as the normal B cell maturation processes. (biomedcentral.com)
DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. (bmbreports.org)

Pembrolizumab disrupts the PD-1/PD-L1 immune checkpoint pathway that modulates the human immune system's natural anticancer activity. (medpagetoday.com)

Unrepaired or incorrectly repaired DNA damage may lead to loss of heterozygosity, mutations, deletions, genomic rearrangements and chromosome loss. (cea.fr)
O'Donnell's laboratory studies these DNA metabolic mechanisms with the goal of understanding how the protein gears of DNA duplication act together with signal processes that function with repair and recombination factors to ensure genomic integrity. (rockefeller.edu)
Genomic instability is a hallmark of cancer and is regulated by the balance between DNA damage and repair (Aguilera and Garcia-Muse, 2013). (villajoyosacf.info)

His research focusses on targeted therapies for DNA repair defective cancers, synthetic lethality and drug resistant cancers. (biomedcentral.com)

This instability is partly caused by the uncontrolled reactions of the various DNA repair pathways (e.g. homologous recombination and non-homologous end joining). (umcg.nl)

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 proteostasis network (PN) is an assembly of distinct dynamic molecular pathways that control the functionality of the proteome (proteome homeodynamics) during protein synthesis, folding, trafficking, and degradation. (hindawi.com)
Studies the molecular mechanisms of DNA replication, recombination, and repair. (rockefeller.edu)
Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. (springer.com)

These studies can be expected to provide new insights into eukaryotic replication, repair, and epigenetic inheritance. (rockefeller.edu)

Moreover, nonreversible mitochondrial damage targets the organelle to a specific autophagic removal, namely, mitophagy. (hindawi.com)
Therefore, a metabolic shift from mitochondrial respiration to the glycolytic pathway occurs during OB differentiation. (nih.gov)

consequently cells have evolved a variety of mechanisms to repair double-strand breaks (DSBs). (brandeis.edu)
Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways. (thermofisher.com)
In all organisms, two different mechanisms are used to repair DSBs: Homologous recombination (HR) and non-homologous end joining (NHEJ). (cea.fr)
Finally, we showed that ssDNA lesions are converted to toxic DSBs in cells lacking functional ataxia telangiectasia mutated (ATM), likely due to failure to form 53BP1 bodies and/or a role for ATM in SSB repair or fork protection [ 14 ]. (nature.com)

Thus, caspase-2 activation during replication stress engages a pathway distinct from that engaged by cytokinesis failure. (nature.com)

NHEJ simply religates the broken ends whereas during HR a DNA break is repaired by copying homologous sequences present elsewhere in the genome. (cea.fr)

Rad17 is a budding yeast checkpoint protein. (embl.de)

Most patients had 3 or more actionable mutations affecting key cancer regulatory networks including mitogenic signalling pathways, DNA-damage repair pathways and cell cycle checkpoints. (businesswire.com)
DNA damage predisposes normal cells and transforms into cancer cell mutations with expression of antigenic determinants related to cancer cell life cycle initiation and survival. (medium.com)

DNA damage in the maintenance of genome integrity and control of the MDM2-p53 axis. (villajoyosacf.info)

Rad3 phosphorylates rad26 which is required to initiate, but not maintain the checkpoint. (wikipedia.org)

DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. (bmbreports.org)
Homologous recombination is the main mechanism to repair DNA lesions that block replication forks and fill ssDNA gaps left behind the fork [11]. (nature.com)
The mechanisms by which isocyanates cause asthma remain unclear, hampering disease prevention, diagnosis, and treatment.7 It is assumed the reactive nature of N=C=O groups underlies isocyanate asthma, with a hapten-based mechanism as the most obvious pathway to pathogenesis.8 However, the critical "self" reaction targets for isocyanate in vivo remain uncertain. (cdc.gov)

Notably, changes including elevated levels of expression of Kras and mmu-miR-155 and the repression of Socs1 were observed following genotoxic damage, reflecting induction of a cancer-prone phenotype. (biomedcentral.com)

Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. (tocris.com)
Several pathways involved in cell cycle and DNA repair were affected upon NV651 treatment. (lu.se)

Subcommittee report on biological indicators of organ damage. (cdc.gov)

His lab studies how the replisome interacts with DNA repair and cell cycle checkpoint machinery, how initiation of replication is directed by nucleosomes, and how replication forks perform nucleosome inheritance, the process by which nucleosomes (the fundamental structural unit of chromosomal DNA) are passed down from parental to daughter DNA during replication. (rockefeller.edu)
We propose a model where caspase-2 regulates the cell cycle and protects DNA replication forks to prevent DNA damage accrual in a pathway distinct from its apoptotic role. (nature.com)

Surveillance is a key control integrated in many multi-functions and mechanisms including DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. (medium.com)
When repair is completed the machinery needs to be disassembled and the DDR turned off. (umcg.nl)

If caspase-2 regulates cell division through the same pathway, it would be expected to phenocopy the cell cycle results of caspase-2 null cells. (nature.com)
Consistent with our evidence that caspase-2 regulates a replication checkpoint, the chromosomal aberrations detected in caspase-2-deficient cells are not repaired before metaphase. (nature.com)

Microsatellite integrity in the genome is believed to be maintained by the mismatch repair (MMR) system, which corrects single base mismatches and insertion-deletion loops on the nascent DNA strand ( Kunkel 1995 ). (medium.com)

We have focused a lot of attention on yeast mating-type gene switching ( MAT switching) as an example of DSB repair that we can study in great detail. (brandeis.edu)

This "in vivo biochemistry" approach has enabled us to demonstrate that there are in fact several independent, competing pathways of homologous recombination, each with its own genetic requirements. (brandeis.edu)
Catastrophic genetic damage can occur if cells progress to the next phase of the cell cycle before the previous phase is properly completed. (tocris.com)
HR comprises different pathways: gene conversion (GC) that accurately repair the lesion by copying the homologous sequence, single strand annealing (SSA) or break induced replication (BIR) that can both lead to loss of genetic information. (cea.fr)
MSI-H and dMMR are types of genetic abnormalities that affect cells' internal mechanisms to repair DNA damage. (medpagetoday.com)

In general, NHEJ is the preferred pathway in the G1 phase of the cell cycle, while HR is favored in S and G2 phases. (cea.fr)

Comparing these transcriptional responses provides a greater understanding of the mechanisms cells use in the differentiation between types of DNA damage and the potential consequences of different sources of damage. (biomedcentral.com)
It is known to halt cancer cell proliferation and the propagation of DNA damage and can also initiate DNA repair mechanisms. (medium.com)

I used immunofluorescence imaging of yH2AX (a histone variant present in damaged DNA) and comet assay to track DNA integrity. (braintumour.ca)
We encourage submissions of work that expands the mechanistic knowledge of DNA damage, repair, integrity, and stability as well as research that translates these concepts to ultimately target cancer at the bedside. (biomedcentral.com)
In this Collection, guest edited by Christopher Lord and Timothy Yap, we aim to highlight insights that expand upon our mechanistic knowledge of DNA damage, repair, integrity, and stability as well as research that leverages these concepts to ultimately target cancer at the bedside. (biomedcentral.com)

RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. (nature.com)
Guillermina's pioneering work in genetics has paved the way for innovative research at MD Anderson and at cancer centers around the world," said President Peter WT Pisters, M.D. "We are proud to count her among our most distinguished faculty, and we are excited to see her recognized by our peers for her transformative work in outlining the p53 pathway. (mdanderson.org)
Failure to properly repair this damage can lead to detrimental health effects, such as uncontrolled cell death and cancer formation. (biomedcentral.com)
This is why only isolated DNA repair signaling is inactivated in cancer cells. (bmbreports.org)
As detailed on our website, the G&E Program tackles foundational questions in development and disease that can be grouped into five research areas: epigenetics, developmental genetics, human genetics, cancer genetics, and genome maintenance and repair. (uth.edu)
The p53 network is known as a crucial induction pathway involved in cancer defense. (medium.com)
Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (diff.org)
Pilot clinical trial and phenotypic analysis in chemotherapy-pretreated, metastatic triple-negative breast cancer patients treated with oral TAK-228 and TAK-117 (PIKTOR) to increase DNA damage repair deficiency followed by cisplatin and nab paclitaxel. (cdc.gov)

These checkpoints may stop the cell cycle after DNA damage, loss of DNA replication or disruption of the mitotic spindle, in order for repair processes to take place. (tocris.com)

As a transcription factor whose expression is increased by DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (medscape.com)

By comparing the transcriptional responses to both types of DNA damage, we can compare the similarities in the responses to damage as well as the differences induced by genotoxic damage. (biomedcentral.com)
Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. (bmbreports.org)

The lab's findings also provide insights into how replisomes achieve the asymmetric inheritance needed for development, and how they participate in DNA damage checkpoint control pathways. (rockefeller.edu)

1993. Protective effects of chlorogenic acid, curcumin and beta-carotene against gamma-radiation-induced in vivo chromosomal damage. (cdc.gov)

However, we did not observe any MDM2 cleavage or caspase-2-dependent p21 expression following exposure to DNA damage or replication stress. (nature.com)

p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. (kegg.jp)

Recently we used a modification of this system to study the mutation rate associated with DSB repair. (brandeis.edu)

Anatomy19

Organisms7

Diseases16

Chemicals and Drugs112

Analytical, Diagnostic and Therapeutic Techniques and Equipment17

Phenomena and Processes97

Disciplines and Occupations1

Information Science3

Health Care3

Kinase12

Chk13

Alterations13

Apoptosis10

Genes10

Proteins25

Tumor6

Activates1

Cellular6

Ionizing radiation3

Chromosomes2

Arrest5

Inhibitor2

Nucleotide excisi2

Kinases6

Apoptotic pathway1

Inhibitors2

Defects6

Mitosis2

Response4

Immune checkpoint1

Genomic3

Defective1

Instability1

Sites of DNA damage1

Molecular3

Eukaryotic1

Mitochondrial2

DSBs4

Activation1

Homologous sequences1

Rad171

Mutations2

Genome integrity1

Phosphorylates1

Mechanism3

Phenotype1

Cell cycle and DNA repair2

Biological1

Replication forks2

Machinery2

Regulates2

Mismatch repair1

Yeast1

Genetic4

NHEJ1

Mechanisms2

Integrity3

Cancer8

Spindle1

Transcription1

Induced by genotoxic2

Control1

Chromosomal1

Mdm21

Targets1

Mutation1