• 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)
  • In this study, we show that Tip60 is required for the early DNA damage response (DDR) to UV, including the phosphorylation of histone 2AX, c-Jun N-terminal kinases (JNKs), and ataxia telangiectasia-related substrates. (rupress.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • It may represent a viable target population for immune checkpoint and DNA damaging treatment. (almacgroup.com)
  • This may provide a therapeutic rationale for immune-checkpoint targeted therapies in the context of DNA damage response deficiency in cancer. (almacgroup.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)
  • 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)
  • 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)
  • 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)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)
  • Mammalian oocytes are arrested in the dictyate stage of meiotic prophase I for long periods of time, during which the high concentration of the p53 family member TAp63α sensitizes them to DNA damage-induced apoptosis. (elifesciences.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)
  • 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)
  • This means that once the switch to the active form is triggered there is no delay waiting for other proteins to be made, which makes oocytes extremely sensitive to DNA damage. (elifesciences.org)
  • 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)
  • 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)
  • Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. (springer.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)
  • In addition to physiologic breaks, lymphocytes are exposed to a variety of genotoxic damage from exogenous sources. (biomedcentral.com)
  • Chemokine release is dependent on activation of the cGAS-STING-IRF3 pathway which is constitutively activated in DNA repair deficient cells, or by exogenous DNA damaging agents. (almacgroup.com)
  • UV irradiation represents a major challenge to genomic integrity throughout the evolution of terrestrial organisms, resulting in the development of specific mechanisms that govern the cellular response to UV-induced DNA damage. (rupress.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • The novel identification of chemotherapy-mediated selection for an angiogenic phenotype in EOC, through upregulation of the PDGFR-VEGF-A signalling pathway. (almacgroup.com)
  • 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)
  • However, despite success against numerous non-neural cancers, its use in the treatment of pediatric and adult brain tumours has had mixed results as the neurobiology of the Top1-associated DNA repair pathways and the functions of the many of the key enzymes remain poorly understood. (braintumour.ca)
  • 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)
  • Failure to properly repair this damage can lead to detrimental health effects, such as uncontrolled cell death and cancer formation. (biomedcentral.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)
  • 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)
  • TAp63α is kept in an inactive and exclusively dimeric state but undergoes rapid phosphorylation-induced tetramerization and concomitant activation upon detection of DNA damage. (elifesciences.org)
  • Moreover, nonreversible mitochondrial damage targets the organelle to a specific autophagic removal, namely, mitophagy. (hindawi.com)
  • Germ cells - from which egg cells and sperm cells develop - are particularly vulnerable as they contain sensitive quality control mechanisms that kill any cell that contain damaged DNA. (elifesciences.org)
  • 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)
  • 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)
  • Using a combination of biophysical methods as well as cell and ovary culture experiments we explain how TAp63α is kept inactive in the absence of DNA damage but causes rapid oocyte elimination in response to a few DNA double strand breaks thereby acting as the key quality control factor in maternal reproduction. (elifesciences.org)
  • DNA damage response deficient human breast cancers are associated with CD8+ and CD4+ lymphocytic infiltration. (almacgroup.com)
  • Resection is accompanied by the binding of replication protein A (RPA) to the 3' single-stranded overhangs, which helps recruiting the checkpoint complexes. (cea.fr)
  • The overall goal of my laboratory is to understand the signals that regulate the p53 pathway and the consequences of expressing wild-type or mutant p53. (mdanderson.org)
  • Activation of the cGAS-STING-IRF3 pathway is cell cycle specific and is associated with an accumulation of cytosolic DNA in the S-phase of the cell cycle. (almacgroup.com)
  • Activation of the cGAS-STING-IRF3 pathway is associated with expression of the immune-checkpointinggene PD-L1 which may prevent immune-mediated tumorcell death. (almacgroup.com)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • Here we compare transcriptional responses to physiological DNA breaks with responses to genotoxic DNA damage induced by ionizing radiation. (biomedcentral.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)
  • 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)
  • 1993. Protective effects of chlorogenic acid, curcumin and beta-carotene against gamma-radiation-induced in vivo chromosomal damage. (cdc.gov)
  • Peritoneal stomata constitute the principal pathways for the drainage of intraperitoneal contents from the PERITONEAL CAVITY to the LYMPHATIC SYSTEM. (bvsalud.org)
  • Unrepaired or incorrectly repaired DNA damage may lead to loss of heterozygosity, mutations, deletions, genomic rearrangements and chromosome loss. (cea.fr)
  • The irradiation and chemotherapy drugs that are used to destroy cancer cells also damage healthy cells. (elifesciences.org)
  • Intrinsic factors include chronically activated proliferative, invasive, and antiapoptotic signaling pathways. (springer.com)
  • A protein called p63, which is closely related to another protein that suppresses the formation of tumors, plays an essential role in detecting and responding to DNA damage. (elifesciences.org)
  • The protein then switches to an active form when DNA damage is detected to trigger the process of cell self-destruction. (elifesciences.org)
  • 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)
  • 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)