Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Biochem Biophys Res Commun. 2014 Jun 13;448(4):385-9. doi: 10.1016/j.bbrc.2014.04.109. Epub 2014 Apr 30.
Phosphorylation of Orc2, one of the six subunits of the origin recognition complex (ORC), by cyclin A/CDK2 during S phase leads to the dissociation of Orc2, Orc3, Orc4, and Orc5 subunits (Orc2-5) from human chromatin and replication origins. Dephosphorylation of the phosphorylated Orc2 by protein phosphatase 1 (PP1) is accompanied by the binding of the dissociated subunits to chromatin. Here we show that PP1 physically interacts with Orc2. The binding of PP1 to Orc2 and the dephosphorylation of Orc2 by PP1 occurred in a cell cycle-dependent manner through an interaction with 119-KSVSF-123, which is the consensus motif for the binding of PP1, of Orc2. The dephosphorylation of Orc2 by PP1 is required for the binding of Orc2 to chromatin. These results support that PP1 dephosphorylates Orc2 to promote the binding of ORC to chromatin and replication origins for the subsequent round of the cell cycle.
磷酸化的 Orc2，六个亚基的起源识别复合物（ORC）之一，由细胞周期蛋白 A/CDK2 在 S 期导致 Orc2、Orc3、Orc4 和 Orc5 亚基（Orc2-5）从人类染色质和复制起点的解离。磷酸化的 Orc2 由蛋白磷酸酶 1（PP1）去磷酸化伴随着解离的亚基与染色质的结合。在这里，我们显示 PP1 与 Orc2 物理相互作用。PP1 与 Orc2 的结合和 PP1 对 Orc2 的去磷酸化通过与 Orc2 的 119-KSVSF-123 相互作用以细胞周期依赖性方式发生，这是 PP1 结合的共有基序。PP1 对 Orc2 的去磷酸化对于 Orc2 与染色质的结合是必需的。这些结果支持 PP1 去磷酸化 Orc2 以促进 ORC 与染色质和复制起点的结合，从而进行细胞周期的下一轮。
