Nek1 与 Ku80 相互作用，以协助复制因子的染色质加载和 S 期进程。
Nek1 interacts with Ku80 to assist chromatin loading of replication factors and S-phase progression.
机构信息
Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, USA.
出版信息
Cell Cycle. 2013 Aug 15;12(16):2608-16. doi: 10.4161/cc.25624. Epub 2013 Jul 10.
Abstract
NIMA-related kinases (Neks) play divergent roles in mammalian cells. While several Neks regulate mitosis, Nek1 was reported to regulate DNA damage response, centrosome duplication and primary cilium formation. Whether Nek1 participates in cell cycle regulation is not known. Here we report that loss of Nek1 results in severe proliferation defect due to a delay in S-phase of the cell cycle. Nek1-deficient cells show replication stress and checkpoint activation under normal growth conditions. Nek1 accumulates on the chromatin during normal DNA replication. In response to replication stress, Nek1 is further activated for chromatin localization. Nek1 interacts with Ku80 and, in Nek1-deficient cells chromatin localization of Ku80 and several other DNA replication factors is significantly reduced. Thus, Nek1 may facilitate S-phase progression by interacting with Ku80 and regulating chromatin loading of replication factors.
摘要
NIMA 相关激酶（Neks）在哺乳动物细胞中发挥不同的作用。虽然有几种 Neks 调节有丝分裂，但据报道 Nek1 调节 DNA 损伤反应、中心体复制和初级纤毛形成。Nek1 是否参与细胞周期调控尚不清楚。在这里，我们报告说，由于细胞周期 S 期的延迟，Nek1 的缺失导致严重的增殖缺陷。在正常生长条件下，Nek1 缺陷细胞表现出复制应激和检查点激活。Nek1 在正常 DNA 复制过程中积累在染色质上。响应复制应激，Nek1 进一步被激活以进行染色质定位。Nek1 与 Ku80 相互作用，在 Nek1 缺陷细胞中，Ku80 和其他几种 DNA 复制因子的染色质定位显著减少。因此，Nek1 可能通过与 Ku80 相互作用并调节复制因子的染色质加载来促进 S 期的进展。
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