v-Src 抑制 Rad17 和 Rad9 之间的相互作用，并诱导复制叉崩溃。

v-Src inhibits the interaction between Rad17 and Rad9 and induces replication fork collapse.

机构信息

Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.

出版信息

Biochem Biophys Res Commun. 2014 Jul 18;450(1):885-90. doi: 10.1016/j.bbrc.2014.06.078. Epub 2014 Jun 24.

DOI:10.1016/j.bbrc.2014.06.078

PMID:24971543

Abstract

ATR-dependent DNA damage checkpoint is crucial to maintain genomic stability. Recently, we showed that Src family kinases suppress ATR-dependent checkpoint signaling in termination of DNA damage checkpoint. However, the precise molecular mechanism is unclear. Therefore, we examined the role of oncogenic v-Src on ATR-Chk1 signaling. We show that v-Src suppresses thymidine-induced Chk1 phosphorylation and induces replication fork collapse. v-Src inhibits interaction between Rad17 and Rad9 in chromatin fraction. By contrast, v-Src does not inhibit RPA32 phosphorylation, ATR autophosphorylation, or TopBP1-Rad9 interaction. These data suggest that v-Src attenuates ATR-Chk1 signaling through the inhibition of Rad17-Rad9 interaction.

摘要

ATR 依赖性 DNA 损伤检查点对于维持基因组稳定性至关重要。最近，我们发现 Src 家族激酶在 DNA 损伤检查点终止时抑制 ATR 依赖性检查点信号。然而，确切的分子机制尚不清楚。因此，我们研究了致癌 v-Src 对 ATR-Chk1 信号的作用。我们发现 v-Src 抑制胸苷诱导的 Chk1 磷酸化并诱导复制叉崩溃。v-Src 在染色质部分抑制 Rad17 和 Rad9 之间的相互作用。相比之下，v-Src 不抑制 RPA32 磷酸化、ATR 自身磷酸化或 TopBP1-Rad9 相互作用。这些数据表明，v-Src 通过抑制 Rad17-Rad9 相互作用来减弱 ATR-Chk1 信号。