Pathways of DNA double-strand break repair during the mammalian cell cycle.
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Cites background from "Pathways of DNA double-strand break..."
...Both of these E3 ligases ubiquitinate H2AX, which then serves as a docking site for 53BP1 and BRCA1....
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...…ATM activation, targeted phosphorylation of H2AX, chromatin PARylation, MDC1 recruitment and finally recruitment of 53BP1 and BRCA1 [Rogakou et al., 1998; Rothkamm et al., 2003; Gottschalk et al., 2009; Chou et al., 2010; Lukas et al., 2011; Price and D’Andrea, 2013; Liu et al., 2014]....
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...Interestingly, both 53BP1 and BRCA1 exhibit an antagonistic influence on each other and 53BP1 depletion rescues embryonic lethal- ity of BRCA1 null mice [Xie et al., 2007; Cao et al., 2009; Bunting et al., 2010]....
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...In the S/G2 phase where HR is predominant, BRCA1 (recruited by ubiquitinated chromatin) successfully counteracts 53BP1 and initiates ubiquitination of the downstream component, CtIP [Yu et al., 2006; Chapman et al., 2012]....
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...Chromatin modification is the first event that registers the presence of a DSB and triggers a cascade of events including ATM activation, targeted phosphorylation of H2AX, chromatin PARylation, MDC1 recruitment and finally recruitment of 53BP1 and BRCA1 [Rogakou et al., 1998; Rothkamm et al., 2003; Gottschalk et al., 2009; Chou et al., 2010; Lukas et al., 2011; Price and D’Andrea, 2013; Liu et al., 2014]....
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References
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"Pathways of DNA double-strand break..." refers background in this paper
...If left unrepaired, DSBs can result in permanent cell cycle arrest, induction of apoptosis, or mitotic cell death caused by loss of genomic material (37); if repaired incorrectly, they can lead to carcinogenesis through translocations, inversions, or deletions (21, 67)....
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3,349 citations
"Pathways of DNA double-strand break..." refers background in this paper
...2B), we incubated cells from 30 min before until 30 min after irradiation in the presence of 200 M phosphatidylinositol 3-kinase inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) (68)....
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...Therefore, cells were incubated in the presence of the phosphatidylinositol 3-kinase inhibitor LY294002 (68), which inactivates DNA-PKcs....
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2,451 citations
"Pathways of DNA double-strand break..." refers background or methods in this paper
...The induction and repair of individual IR-induced DSBs in * Corresponding author....
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...Here we used -H2AX focus formation to quantify the repair of IR-induced DSBs. Initial studies showed a close relationship between the number of -H2AX foci and the number of expected DSBs after treatment with IR (46)....
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...This finding is the first direct demonstration of a contribution of HR to the repair of IR-induced DSBs....
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...Thus, the relative importance of HR in repairing IR-induced DSBs increases from G1 through S and into late S/G2....
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...In our laboratory, the induction and repair of IR-induced DSBs in primary human fibroblasts in the G1 phase were studied by examining -H2AX focus formation in parallel with PFGE assays (49)....
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1,604 citations
"Pathways of DNA double-strand break..." refers background or methods in this paper
...PFGE....
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...Importantly, G1phase HR-defective irs1SF cells had almost normal DSB repair kinetics for both -H2AX and PFGE end points....
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...Because cell survival after aphidicolin treatment is also reduced the most in irs1SF cells, it appears that aphidicolin-induced DSBs are primarily repaired by HR. DSBs arising from replication fork blockage after UV irradiation result in -H2AX focus formation (31, 71), and PFGE measurements show that aphidicolin induces DSBs specifically during the S phase (50)....
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...By using -H2AX focus analysis as an approach for DSB repair measurements, Rothkamm and Löbrich conducted the first study of DSB repair in mammalian cells by using physiologically relevant radiation doses (49)....
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...In our laboratory, the induction and repair of IR-induced DSBs in primary human fibroblasts in the G1 phase were studied by examining -H2AX focus formation in parallel with PFGE assays (49)....
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