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  • CHK1
  • After radiation exposure, the G 2 -M phase accumulation and the preceding repression of the G 2 phase regulatory factors Polo-like kinase-1 and cyclin B1 required intact G 2 checkpoint signaling through the checkpoint kinase CHK1, whereas the similar phenotypic changes observed with HDAC inhibition did not. (aacrjournals.org)
  • Here we show that human cells lacking Chk1 exhibit defects in both the ionizing radiation (IR)-induced S and G 2 checkpoints. (pnas.org)
  • In addition, loss of Chk1 resulted in the accumulation of a hypophosphorylated form of the Cdc25A protein phosphatase, and Chk1-deficient cells failed to degrade Cdc25A after IR. (pnas.org)
  • The IR-induced S and G 2 checkpoints were partially restored in Chk1-deficient cells when Cdc25A accumulation was interfered with. (pnas.org)
  • Although chk1 is not an essential gene in fission yeast, it is essential in mice ( 1 , 3 , 8 , 9 ). (pnas.org)
  • Evidence that Chk1 contributes to G 2 checkpoint control in human cells comes from studies showing that agents such as UCN-01 and SB-218078, which are potent inhibitors of Chk1, abrogate G 2 checkpoint function in human cells ( 10-12 ). (pnas.org)
  • The contribution made by Chk1 to the IR-induced DNA damage checkpoint in humans remains controversial. (pnas.org)
  • In addition, human Chk1 has been proposed to regulate the stability of the Cdc25A protein phosphatase in UV-damaged cells ( 19 ). (pnas.org)
  • In this study, we investigated the contribution made by human Chk1 to the cell division cycle both in the absence and presence of checkpoint activation. (pnas.org)
  • We report that cells deficient in human Chk1 exhibit radio-resistant DNA synthesis and do not delay in G 2 after IR treatment. (pnas.org)
  • We provide evidence that Chk1 directly regulates Cdc25A throughout an unperturbed cell cycle, and that the integrity of the Chk1/Cdc25A regulatory pathway is essential for cells to respond appropriately to ionizing radiation. (pnas.org)
  • amino
  • Unequal usage of synonymous codons in the gene transcript for an amino acid is known as codon usage bias (CUB). (bioportfolio.com)
  • In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. (mdpi.com)
  • mutation
  • The musN227 mutation partially suppresses the poor growth and DNA damage sensitivity of uvsB mutants. (genetics.org)
  • Notably, the failure of uvsB mutants to restrain septum formation in the presence of DNA damage is suppressed by the musN227 mutation. (genetics.org)
  • It is not yet clear whether women with ovarian cancer who have a mutation in either of the BRCA genes are more susceptible to treatment with platinum-based chemotherapy and may therefore have a better response and overall survival. (cancernetwork.com)
  • FOXA2 gene mutation in a patient with congenital complex pituitary hormone deficiency. (bioportfolio.com)
  • Fibroblasts isolated from an Amyotrophic Lateral Sclerosis (ALS)-patient carrying a mutation in Matrin-3 (p.Q66K -MATR3) gene were reprogrammed to the pluripotency stage by using non-integrating episo. (bioportfolio.com)
  • The purpose of this study is to find a gene or its mutation (an altered gene) that puts individuals at risk for developing HE or HPP. (bioportfolio.com)
  • The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE). (bioportfolio.com)
  • A mutation that results in an increase in a gene's activity or in acquiring a new molecular function or a new pattern of gene expression. (bioportfolio.com)
  • The use of techniques that produce a functional MUTATION or an effect on GENE EXPRESSION of a specific gene of interest in order to identify the role or activity of the gene product of that gene. (bioportfolio.com)
  • A mutation that causes a decrease in or elimination of a gene product's activity. (bioportfolio.com)
  • This patient had a germ-line homozygous mutation (657del5) of the NBS1 gene ( 11 ). (aacrjournals.org)
  • This single point mutation mediates reduced response to estradiol-induced cell proliferation but increased resistance to tamoxifen-induced growth inhibition. (biomedcentral.com)
  • The general paradigm is that a tumor is initiated from a normal colonocyte stem cell that has sustained genetic damage over time due to the local environment and any germline genetic mutation that has been inherited. (nih.gov)
  • For example, Werner's syndrome, a disease associated with premature human ageing, is associated with a mutation in a gene encoding a DNA repair protein. (ncl.ac.uk)
  • Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAF V600E mutation and PTEN loss, and H3, harboring WT (wild-type) BRAF and PTEN loss, with the MAPK (BRAF) inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. (mdpi.com)
  • Identification of 2 distinct deleted regions on the short arm of chromosome 1 and rare mutation of the CDKN2C gene from 1 p32 in oligodendroglial tumors. (thefreedictionary.com)
  • cyclin-depend
  • Human ES cells rapidly and robustly (>200-fold) induce the cyclin dependent kinase (CDK) inhibitor p21(WAF1/CIP1) upon gamma-irradiation. (umassmed.edu)
  • chromosome
  • A gene on chromosome 3q22-q24 that encodes a protein belonging to the PI3/PI4-kinase family, which is closely related to ATM, the protein kinase encoded by the gene mutated in ataxia telangiectasia. (thefreedictionary.com)
  • The gene mutated in this syndrome is NBS1 , located at chromosome 8q21 ( 9 ). (aacrjournals.org)
  • This can involve the loss or gain of whole chromosomes or parts of chromosomes, chromosome translocations, and gene amplifications. (aacrjournals.org)
  • molecular
  • Among molecular cell cycle-targeted drugs currently in the pipeline for testing in early-phase clinical trials, HDAC inhibitors may have therapeutic potential as radiosensitizers. (aacrjournals.org)
  • The implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct molecular link between DSB repair and cell cycle checkpoint functions. (nih.gov)
  • Collectively, these data suggest that expression of mLEEK and the subsequent upregulation molecular chaperones primes cells to accommodate the increased need for protein folding upon ER stress and prevents induction of the UPR. (stanford.edu)
  • Our lab uses genetic, molecular and biochemical approaches to understand the interplay between DNA damage responses and telomeres in the model organism Saccharomyces cerevisiae (budding yeast). (ncl.ac.uk)
  • Molecular Biology of the Cell 2016, 27 (17), 2784-2801. (ncl.ac.uk)
  • mitotic
  • Following pretreatment with the HDAC inhibitor, the efficiency of clonogenic regrowth after irradiation was reduced, which is in accordance with the concept of increased probability of mitotic cell death when the chromatin structure is disrupted. (aacrjournals.org)
  • instability
  • Loss or inactivation of ATM leads to A-T, an autosomal recessive disorder characterized by neuronal degeneration, particularly the loss of cerebellar granule and Purkinje cells, immunodeficiency, genomic instability, radiosensitivity, and cancer predisposition. (jneurosci.org)
  • Checkpoint loss results in genomic instability and has been implicated in the evolution of normal cells into cancer cells. (sciencemag.org)
  • We use mathematical models to determine the conditions under which selection favors instability, and when stable cells are advantageous. (aacrjournals.org)
  • A high DNA hit rate can select against instability and result in the persistence of stable cells. (aacrjournals.org)
  • Substantial progress has been made to identify causes of chromosomal instability in colorectal cells and to determine the effects of the different forms of genomic instability on the biological and clinical behavior of colon tumors. (nih.gov)
  • In addition to genomic instability, epigenetic instability results in the aberrant methylation of tumor suppressor genes. (nih.gov)
  • inhibitor
  • Essentially, in tumor cells with intact p53 function, DNA damage leads to rapid p53 stabilization by posttranslational protein modifications as well as induction of the G 1 phase inhibitor p21 ( 7 ). (aacrjournals.org)
  • A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor. (sigmaaldrich.com)
  • Similarly, after DNA damage, RNR activity is increased by Dun1-dependent phosphorylation of the Rnr1 inhibitor Sml1 ( 6 ). (aacrjournals.org)
  • We investigated the mechanism of NU7441, a highly selective DNA-PK inhibitor, in NHEJ-competent mouse embryonic fibroblast (MEF) cells and NHEJ-deficient cells and explored the feasibility of its application in radiosensitizing nasopharyngeal carcinoma (NPC) cells. (spandidos-publications.com)
  • NU7441, a highly potent and selective DNA-PK inhibitor, has been reported to effectively radiosensitize several human cancer cells ( 15 - 22 ). (spandidos-publications.com)
  • chromatin
  • GO annotations related to this gene include chromatin binding and RNA polymerase II core binding . (genecards.org)
  • Thus, these two related chromatin remodelers have distinct roles in DSB repair and checkpoint activation. (embopress.org)
  • To overcome this nucleosome barrier, cells possess histone‐modifying enzymes and chromatin remodeling complexes ( Marmorstein, 2001 ). (embopress.org)
  • Notably, the highly mutated estrogen receptor binding sites are associated with more frequent chromatin loop contacts and the associated distal genes are expressed at higher level. (biomedcentral.com)
  • Using a CRISPR base editor, we show that the recurrent C→T conversion at the ZNF143 locus results in decreased TF binding, increased chromatin loop formation, and increased expression of multiple distal genes. (biomedcentral.com)
  • embryonic
  • 293T cells (human embryonic kidney) were cultured in DMEM supplemented with 10% fetal bovine serum at 37°C in 10% CO 2 . (aacrjournals.org)
  • NIH3T3 cells (mouse embryonic fibroblast) were cultured in DMEM supplemented with 10% calf serum at 37°C in 10% CO 2 . (aacrjournals.org)
  • Rapid self-renewal of human embryonic stem (ES) cells (NIH designation WA01 and WA09) is accommodated by an abbreviated cell cycle due to a reduction in the G1 phase. (umassmed.edu)
  • genetic
  • How are genetic conditions and genes named? (nih.gov)
  • These genetic manipulations could present a "proof of principle" or validation of the importance of the target genes to the development of cancer. (nih.gov)
  • The genetic material of cells is subject to stress and damage as a result of environmental agents or the production of oxidative radicals during metabolism. (aacrjournals.org)
  • They differ in the probability with which they repair genetic damage. (aacrjournals.org)
  • responses
  • Importantly, all of these responses are detected in the nuclei of granule and Purkinje cells, suggesting that nuclear ATM functions in these cells similar to other cell types. (jneurosci.org)
  • Both proteasome and vacuolar-mediated protein degradation have been implicated in stress responses and components of both pathways are associated with the reaction to and recovery from DNA-damaging agents ( 14-16 ). (aacrjournals.org)
  • Since the biochemical mechanisms underlying DNA-damage responses are largely conserved between yeast and human cells our studies in a simple, yet powerful model system, are of direct relevance to human health. (ncl.ac.uk)
  • modulate
  • We hypothesized that SNPs in DSB signalling genes may modulate predisposition to bladder cancer and influence the effects of environmental exposures. (biomedcentral.com)
  • Apart from a possible effect for one MRE11 3'UTR SNP, our study does not support the hypothesis that SNPs in DSB signaling genes modulate predisposition to bladder cancer. (biomedcentral.com)
  • organisms
  • Thus, the BRCT domain is likely to perform critical, yet uncharacterized, functions in the cell cycle control of organisms from bacteria to humans. (epfl.ch)
  • For example, projects may include development of organisms in which genes in key pathways or processes are mutated or in which human transgenes are expressed to simulate changes known to occur in human cancers. (nih.gov)
  • Some examples of genes that are well studied in model organisms and known or strongly suspected of involvement in cancer include oncogenes, proto-oncogenes, some cell cycle and signal transduction genes, and DNA repair genes. (nih.gov)