期刊
CELL CYCLE
卷 2, 期 4, 页码 316-324出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.2.4.468
关键词
cell cycle; checkpoints; cyclin; DNA damage; DNA replication
类别
资金
- Croucher Foundation
- Philip Morris External Research Program
- Research Grants Council
Mammalian DNA replication is an elegantly choreographed process in which multiple components are assembled at the origins to form the prereplication complex. Formation and activation of the prereplication complex requires coordinate actions of G(1) and S phase cyclin-dependent kinases. Cyclin E-CDK2 and cyclin A-CDK2, together with DBF4-CDC7, phosphorylate several components of the prereplication complex and replication machinery. In this review, we summarize the current understanding of the mechanism of initiation of DNA replication in mammalian cells. The roles of cyclin A/E-CDK2 complexes in driving replication, their relationship with other regulators of S phase, and their role in keeping replication to only once per cell cycle will be discussed. In addition, an important issue is the checks and balances that prevent inappropriate DNA replication, and how a breakdown in these checkpoints can lead to genomic instability and cancer. A critical mediator of these checkpoints, ATM, signals through a comprehensive network of proteins leading to CDK2 inhibition thus preventing DNA synthesis. This will be reviewed in addition to other mechanisms involved in the intra-S phase DNA damage checkpoint.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据