γ-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin
By A. Kinner, Wenqi Wu, Christian Staudt, G. Iliakis. Nucleic Acids Research, 2008
1,258 citations recorded by the source corpus.
DNA double-strand breaks (DSBs) are extremely dangerous lesions with severe consequences for cell survival and the maintenance of genomic stability. In higher eukaryotic cells, DSBs in chromatin promptly initiate the phosphorylation of the histone H2A variant, H2AX, at Serine 139 to generate γ-H2AX. This phosphorylation event requires the activation of the phosphatidylinositol-3-OH-kinase-like family of protein kinases, DNA-PKcs, ATM, and ATR, and serves as a landing pad for the accumulation and retention of the central components of the signaling cascade initiated by DNA damage. Regions in chromatin with γ-H2AX are conveniently detected by immunofluorescence microscopy and serve as beacons of DSBs. This has allowed the development of an assay that has proved particularly useful in the molecular analysis of the processing of DSBs. Here, we first review the role of γ-H2AX in DNA damage response in the context of chromatin and discuss subsequently the use of this modification as a surrogate marker for mechanistic studies of DSB induction and processing. We conclude with a critical analysis of the strengths and weaknesses of the approach and present some interesting applications of the resulting methodology.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/e5c61dc43b9bff3530d0f6100c51c76500c7f103
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In Molecular Biology
Citations in the corpus
- γH2AX foci analysis for monitoring DNA double-strand break repair: Strengths, limitations and optimization (2010, background): “Currently, it is unclear whether loss of visible foci precisely correlates with the final step in the rejoining process or whether a delay of 1–2 h occurs due to the additional time required to fully reconstitute the chromatin status.(4)”
- NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. (2009, background): “This phosphorylation is required for DSB signalling and is thought to act as a beacon to recruit and retain DNA repair proteins to the DSB site [206,207].”