53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response to DNA damage.
作者： Tamara A. Mochan , Thanos D. Halazonetis , Richard A. DiTullio , Monica Venere
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摘要: 53BP1 and NFBD1/MDC1 are recruited rapidly to sites of DNA double-strand breaks (DSBs), where they hypothesized function downstream the ataxia-telangiectasia mutated (ATM) checkpoint kinase as "mediators" DSB signaling. To test this hypothesis, we suppressed expression by small interference RNA monitored ATM autophosphorylation at Ser(1981) a marker for activation. Suppression led decreased activation phosphorylation substrates. This phenotype was identical that observed in cells with defective Nbs1 is consistent recent observations identifying component Mre11-Rad50-Nbs1 protein complex. In wild-type Nbs1, suppression had no effect on but associated increased recruitment breaks, suggesting might be compensated activity. Indeed, mutant We conclude DSBs activate through least two independent pathways involving NFBD1/MDC1-Nbs1, respectively.
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