Nek1通过调控Rad54来协调同源重组和复制叉稳定性。
Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability.
作者信息
Spies Julian, Waizenegger Anja, Barton Olivia, Sürder Michael, Wright William D, Heyer Wolf-Dietrich, Löbrich Markus
机构信息
Radiation Biology and DNA Repair, Darmstadt University of Technology, 64287 Darmstadt, Germany.
Section of Microbiology, University of California, Davis, Davis, CA 95616-8665, USA.
出版信息
Mol Cell. 2016 Jun 16;62(6):903-917. doi: 10.1016/j.molcel.2016.04.032. Epub 2016 Jun 2.
Never-in-mitosis A-related kinase 1 (Nek1) has established roles in apoptosis and cell cycle regulation. We show that human Nek1 regulates homologous recombination (HR) by phosphorylating Rad54 at Ser572 in late G2 phase. Nek1 deficiency as well as expression of unphosphorylatable Rad54 (Rad54-S572A) cause unresolved Rad51 foci and confer a defect in HR. Phospho-mimic Rad54 (Rad54-S572E), in contrast, promotes HR and rescues the HR defect associated with Nek1 loss. Although expression of phospho-mimic Rad54 is beneficial for HR, it causes Rad51 removal from chromatin and degradation of stalled replication forks in S phase. Thus, G2-specific phosphorylation of Rad54 by Nek1 promotes Rad51 chromatin removal during HR in G2 phase, and its absence in S phase is required for replication fork stability. In summary, Nek1 regulates Rad51 removal to orchestrate HR and replication fork stability.
无丝分裂A相关激酶1（Nek1）在细胞凋亡和细胞周期调控中已确立其作用。我们发现，人类Nek1通过在G2晚期磷酸化Rad54的Ser572来调节同源重组（HR）。Nek1缺陷以及不可磷酸化的Rad54（Rad54-S572A）的表达会导致Rad51焦点未解决，并导致HR缺陷。相比之下，磷酸化模拟Rad54（Rad54-S572E）促进HR，并挽救与Nek1缺失相关的HR缺陷。尽管磷酸化模拟Rad54的表达对HR有益，但它会导致Rad51从染色质上移除，并导致S期停滞的复制叉降解。因此，Nek1对Rad54的G2特异性磷酸化促进了G2期HR过程中Rad51从染色质上的移除，而其在S期的缺失是复制叉稳定性所必需的。总之，Nek1调节Rad51的移除，以协调HR和复制叉的稳定性。
Zotero 插件