Loading...
  • response
  • In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. (frontiersin.org)
  • The DNA damage response (DDR) is a complex signal transduction pathway that is required for preserving the genetic information encoded by DNA and for ensuring its accurate transmission through generations. (frontiersin.org)
  • cellular
  • We highlight evidence gained into (i) which molecular and cellular pathways of DDR activate immune signaling, (ii) how DNA damage drives chronic inflammation, and (iii) how chronic inflammation causes DNA damage and pathology in humans. (frontiersin.org)
  • ataxia telangi
  • A key component of the DNA damage checkpoint is ATM (ataxia telangiectasia-mutated), a 370-kDa protein kinase ( 58 ). (asm.org)
  • These deficiencies are consistent with reduced expression of components of the ataxia telangiectasia mutated (ATM)-dependent signaling pathway and, in particular, strong upregulation of Wip1, a negative regulator of the ATM pathway. (aacrjournals.org)
  • mammalian
  • Some previous studies of p53 expression and regulation in lower vertebrate species have shown potential differences in its control, in comparison to the better characterized mammalian pathways. (uwaterloo.ca)
  • genetic
  • Further support for genetic interaction between RAD9 and RAD24 comes from study of the modification and activation of Rad53 after damage. (embopress.org)
  • In particular, genetic analysis in C. elegans has identified components of major signaling pathways that underlie diseases of aging such as cancer and Alzheimer's disease, and revealed. (ellisonfoundation.org)
  • Checkpoints are signaling pathways that monitor the integrity and replication status of the genetic material before cells commit to either replicate (in S phase) or segregate (in mitosis) their DNA ( 27 ). (asm.org)
  • The DNA damage response (DDR) is a complex signal transduction pathway that is required for preserving the genetic information encoded by DNA and for ensuring its accurate transmission through generations. (frontiersin.org)
  • sensitivity
  • Activation of the cellular DNA damage response (DDR) is an important determinant of cell sensitivity to cisplatin and other chemotherapeutic drugs that eliminate tumor cells through induction of DNA damage. (aacrjournals.org)
  • Other groups have investigated the sensitivity of homozygous deletion strains to various DNA-damaging treatments. (biomedcentral.com)
  • methyl methanesulfonate
  • To evaluate its biomarker potential for aquatic toxicology studies, two rainbow trout cell lines (RTbrain-W1 and RTgill-W1) were used in dose response experiments using DNA damage checkpoint inducing agents: bleomycin, hydroxyurea, and methyl methanesulfonate. (uwaterloo.ca)
  • DNA damage may occur as a result of many different kinds of damaging agents (for example, methyl-methanesulfonate (MMS), γ-rays and ultraviolet (UV) light). (biomedcentral.com)
  • homologous
  • These enzymes control homologous recombination-dependent and nonhomologous recombination-dependent amplification pathways that act in concert to mediate rapid, directional ribosomal DNA copy number change. (pnas.org)
  • Eukaryotic
  • Eukaryotic cells use a variety of mechanisms to protect themselves from the harmful effects of DNA damage. (ncl.ac.uk)
  • targets
  • Our findings identified deregulation of XPC and CypA as key targets of CsA, and UVB damage and PI3K/AKT activation as two principal drivers for CsA-sensitized skin tumorigenesis, further supporting an immunosuppression-independent mechanism of CsA action on skin tumorigenesis. (aacrjournals.org)
  • Here we report that MDC1 directly binds to NBS1 and targets NBS1 to the sites of DNA damage. (pnas.org)
  • ribosomal
  • Several mechanisms of p53 activation that suggest a special checkpoint controlling ribosomal biogenesis have been proposed, but the exact mechanism remains unclear ( Fumagalli and Thomas, 2011 ). (biologists.org)
  • Cds1
  • S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe. (nih.gov)
  • radiation
  • Preliminary evidence for the order of function for this DNA structure checkpoint pathway(s) has come from analysis of the radiation‐sensitive phenotype of certain mutants. (embopress.org)
  • Radiation and most chemotherapeutic drugs exert their toxicity to tumor cells primarily through induction of DNA damage, which halts cell proliferation and induces cell death. (aacrjournals.org)
  • Other DNA damaging agents are ultraviolet light, ionizing radiation and a large variety of chemical agents ( Hoeijmakers, 2009 ). (frontiersin.org)
  • Cells derived from NBS and ATLD patients are hypersensitive to radiation and display impaired intra-S-phase checkpoint activation ( 1 ⇓ - 3 ), supporting critical roles of this complex in DNA damage response. (pnas.org)
  • double strand
  • Ngo GHP, Lydall D. The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks . (ncl.ac.uk)
  • Disruption of the MDC1-NBS1 interaction results in failure of NBS1 accumulation at DNA double-strand breaks and impairment of intra-S checkpoint activation. (pnas.org)
  • cells
  • Replication stress and DNA damage in cultured cells in non-DBA models can be decreased by exogenous nucleosides. (biologists.org)
  • It is therefore important to investigate whether alterations of the DNA damage-signaling pathway confer chemoresistance in cancer cells and whether pharmacologic manipulation of the DDR pathway can resensitize these cells to cancer therapy. (aacrjournals.org)