Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication.
Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication.
复制标题
非洲爪蟾卵提取物中 Xic1 的降解与 DNA 复制的启动相关。
DOI：
10.1101/gad.985302
复制
发表时间：
2002
影响因子：
10.5
通讯作者：
Newport,John
中科院分区：
文献类型：
--
作者：
You,Zhongsheng;Harvey,Kevin;Kong,Lindsay;Newport,John
CDK 2活性受磷酸化/去磷酸化、亚细胞定位、细胞周期蛋白水平和细胞周期蛋白依赖性激酶抑制剂（CKIs）调节。使用Xenopusegg提取物，我们发现Xenopusp 21 cip 1/p27 kip 1家族成员Xic 1的降解与DNA复制的启动相关联。Xic 1周转需要形成一个复制前复合物（pre-RC）。此外，下游起始因子（包括CDK 2、Cdc 7和Cdc 45，而不是RPA或DNA聚合酶α）是激活降解系统所必需的。Xic 1降解在DNA复制完成后减弱。与哺乳动物细胞中p27 kip 1的降解不同，CDK 2活性不直接参与Xic 1的降解，Xic 1和CDK 2/cyclin E之间的相互作用与Xic 1的周转无关。有趣的是，Xic 1的C-末端区域（162-192）是必不可少的，显然足以在降解之前触发Xic 1泛素化。这些观察结果表明，DNA复制和CKI降解之间存在直接联系。
CDK2 activity is regulated by phosphorylation/dephosphorylation, subcellular localization, cyclin levels, and cyclin dependent kinase inhibitors (CKIs). UsingXenopusegg extracts, we find that degradation of Xic1, aXenopusp21cip1/p27kip1family member, is coupled to initiation of DNA replication. Xic1 turnover requires the formation of a prereplication complex (pre-RC). Additionally, downstream initiation factors including CDK2, Cdc7, and Cdc45, but not RPA or DNA polymerase α, are necessary for activating the degradation system. Xic1 degradation is attenuated following completion of DNA replication. Unlike degradation of p27kip1in mammalian cells, CDK2 activity is not directly involved in Xic1 degradation and interactions between Xic1 and CDK2/cyclin E are dispensable for Xic1 turnover. Interestingly, a C-terminal region (162–192) of Xic1 is essential and apparently sufficient for triggering Xic1 ubiquitination prior to degradation. These observations demonstrate that a direct link exists between DNA replication and CKI degradation.