Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication
Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication
复制标题
DOI：
10.1016/s1097-2765(02)00467-7
复制
发表时间：
2002-03-01
期刊：
影响因子：
16
通讯作者：
Stillman, B
中科院分区：
文献类型：
--
作者：
Méndez, J;Zou-Yang, XH;Stillman, B
真核细胞具有重叠机制，以确保DNA复制仅限于细胞周期的S期。人类起源识别复合物的最大亚基hOrc1p的水平在细胞分裂周期中变化。在快速增殖的细胞中，当细胞退出有丝分裂并形成复制前复合物时，hOrc1p表达并靶向染色质。后来，随着细胞周期蛋白A的积累和细胞进入S期，hOrc1p在染色质上被泛素化，然后降解。hOrc1p破坏通过蛋白酶体发生，并部分通过SCFSkp2泛素连接酶复合物发出信号。其他hORC亚基在整个细胞周期中是稳定的。hOrc1p的调节可能是维持人类细胞倍性的重要机制。
Eukaryotic cells possess overlapping mechanisms to ensure that DNA replication is restricted to the S phase of the cell cycle. The levels of hOrc1p, the largest subunit of the human origin recognition complex, vary during the cell division cycle. In rapidly proliferating cells, hOrc1p is expressed and targeted to chromatin as cells exit mitosis and prereplicative complexes are formed. Later, as cyclin A accumulates and cells enter S phase, hOrc1p is ubiquitinated on chromatin and then degraded. hOrc1p destruction occurs through the proteasome and is signaled in part by the SCFSkp2 ubiquitin-ligase complex. Other hORC subunits are stable throughout the cell cycle. The regulation of hOrc1p may be an important mechanism in maintaining the ploidy in human cells.