Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks.
Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks.
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Lyn 酪氨酸激酶在 DNA 双链断裂恢复过程中促进 ATM 依赖性检查点信号的沉默。
DOI：
10.1016/j.bbrc.2014.08.113
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
N.
中科院分区：
文献类型：
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作者：
Fukumoto;Y.;Kuki;K.;Morii;M.;Miura;T.;Honda;T.;Ishibashi;K.;Hasegawa;H.;Kubota;S.;Ide;Y.;Yamaguchi;N.-t.;Nakayama;Y.;and Yamaguchi;N.
DNA损伤激活DNA损伤检查点和DNA修复机制。DNA损伤反应初始激活后，细胞通过DNA修复的完成和检查点信号的终止恢复到原来的状态。目前，人们对细胞从DNA损伤检查点恢复的过程知之甚少，这一过程被称为检查点恢复。在这里，我们发现Src家族激酶在DNA双链断裂恢复过程中促进共济失调毛细血管扩张突变（ATM）依赖性检查点信号的失活。Src活性的抑制增加了atm依赖性的Chk2和Kap1磷酸化。Src抑制增加了G2期和异步生长期间的ATM信号。shRNA敲低Lyn增加ATM信号。src依赖性核酪氨酸磷酸化抑制atm介导的Kap1磷酸化。这些结果表明Src家族激酶参与导致atm依赖性DNA损伤检查点失活的上游信号传导。
DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphorylation of Chk2 and Kap1. Src inhibition increased ATM signaling both in G2 phase and during asynchronous growth. shRNA knockdown of Lyn increased ATM signaling. Src-dependent nuclear tyrosine phosphorylation suppressed ATM-mediated Kap1 phosphorylation. These results suggest that Src family kinases are involved in upstream signaling that leads to inactivation of the ATM-dependent DNA damage checkpoint.