The DNA-damage response in human biology and disease

By Stephen P. Jackson, J. Bartek. Nature, 2009

5,804 citations recorded by the source corpus.

The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults by endogenous and environmental agents on the DNA. To counter this threat, life has evolved several systems to detect DNA damage, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/86d3bd76ada3d9e9a911e96890f7113663e1b210

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Citations in the corpus

Hallmarks of cancer: the next generation. (2011, neutral): “The telomeres, composed of multiple tandem hexanucleotide repeats, shorten progressively in nonimmortalized cells propagated in culture, eventually losing the ability to protect the ends of chromosomal DNAs from end-to-end fusions; such fusions generate unstable dicentric chromosomes whose resolutio”
Genome editing with engineered zinc finger nucleases (2010, background): “All eukaryotic cells efficiently repair DSBs via the homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathway”
Mechanisms of DNA damage, repair and mutagenesis (2017, neutral): “Unresolved DSBs are implicated in various human disorders and cancers [Jackson and Bartek, 2009].”
53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks (2010, positive): “The ability of PARP inhibitors to selectively kill HR-deficient cells is currently being used in clinical trials for treatment of breast and ovarian cancers where Brca1 or Brca2 is mutated (Fong et al., 2009; Jackson and Bartek, 2009).”
Translational regulation of gene expression during conditions of cell stress. (2010, background): “The decision to undertake a program of repair or cell death is dictated by both the severity and the nature of the DNA damage experienced (Jackson and Bartek, 2009).”
Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. (2013, background): “during tumorigenesis and cannot produce a prolonged cell cycle arrest.(4) This results in”
Oxidative Stress: Harms and Benefits for Human Health (2017, background): “These lesions are promptly repaired, as the results of the rapid activation of DSB damage repair mechanism, most importantly nonhomologous end joining or homologous recombination and the execution of a complex and finely tuned sequelae of those cellular signaling pathways belonging to the DNA damage”
DNA damage and its links to neurodegeneration (2014, neutral): “…cells activate a highly evolved DNA damage response (DDR) that not only detects and repairs damaged DNA, but also coordinates repair with other cellular processes, such as chromatin remodeling, transcription, cell cycle progression (in dividing cells), and apoptosis (Jackson and Bartek, 2009).”
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA non-homologous end-joining (2010, neutral): “1899" language="eng" relation="no"> Because DNA damage represents a formidable challenge to the integrity of genetic material, cells have evolved multifaceted systems, collectively termed the DNA-damage response (DDR), to detect, signal and repair various types of DNA damag”
The MRE11 complex: starting from the ends (2011, background): “Consistent with this, hereditary cancer predisposition, as well as other severe pathologies, results from mutations in DDR gene”