gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin Export

@article{citeulike:3360964, abstract = {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 {gamma}-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 {gamma}-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 {gamma}-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. 10.1093/nar/gkn550}, author = {Kinner, Andrea and Wu, Wenqi and Staudt, Christian and Iliakis, George}, citeulike-article-id = {3360964}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/gkn550}, citeulike-linkout-1 = {http://nar.oxfordjournals.org/cgi/content/abstract/36/17/5678}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18772227}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18772227}, day = {1}, doi = {10.1093/nar/gkn550}, journal = {Nucl. Acids Res.}, keywords = {dna-damage, dna-repair, h2ax}, month = {October}, number = {17}, pages = {5678--5694}, posted-at = {2008-10-01 00:13:44}, priority = {2}, title = {{gamma}-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin}, url = {http://dx.doi.org/10.1093/nar/gkn550}, volume = {36}, year = {2008} }

TY - JOUR ID - citeulike:3360964 L3 - citeulike-article-id:3360964 N2 - 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 {gamma}-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 {gamma}-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 {gamma}-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. 10.1093/nar/gkn550 IS - 17 JF - Nucl. Acids Res. EP - 5694 TI - {gamma}-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin VL - 36 SP - 5678 KW - dna-damage KW - dna-repair KW - h2ax AU - Kinner, Andrea AU - Wu, Wenqi AU - Staudt, Christian AU - Iliakis, George PY - 2008/10/01/ UR - http://dx.doi.org/10.1093/nar/gkn550 ER -