期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/ijms22168796
关键词
DNA replication; mitosis; ubiquitin; SUMO; USP7; CDK1
资金
- MINECO [BFU2014-55168-JIN, RTI2018-093485-B-I00]
- Ramon y Cajal Fellowship from MINECO [RYC-2016-20705]
- European Regional Development Funds (FEDER)
- Spanish Ministry of Science, Innovation and Universities [RTI2018-102204-B-I00]
- European Research Council [ERC-617840]
- Fundacion Ramon Areces-UAM
- LaCaixa Foundation to Pablo Valledor [LCF/BQ/ES18/11670008]
- MINECO to Antonio Galarreta [BES-2015-075758]
Post-translational modification of the DNA replication machinery by ubiquitin and SUMO plays key roles in ensuring the faithful duplication of genetic information. Ubiquitination and SUMOylation not only serve as signals for the extraction of factors from chromatin, but also mediate the disassembly of the replisome and preserve genomic stability in DNA replication.
Post-translational modification of the DNA replication machinery by ubiquitin and SUMO plays key roles in the faithful duplication of the genetic information. Among other functions, ubiquitination and SUMOylation serve as signals for the extraction of factors from chromatin by the AAA ATPase VCP. In addition to the regulation of DNA replication initiation and elongation, we now know that ubiquitination mediates the disassembly of the replisome after DNA replication termination, a process that is essential to preserve genomic stability. Here, we review the recent evidence showing how active DNA replication restricts replisome ubiquitination to prevent the premature disassembly of the DNA replication machinery. Ubiquitination also mediates the removal of the replisome to allow DNA repair. Further, we discuss the interplay between ubiquitin-mediated replisome disassembly and the activation of CDK1 that is required to set up the transition from the S phase to mitosis. We propose the existence of a ubiquitin-CDK1 relay, where the disassembly of terminated replisomes increases CDK1 activity that, in turn, favors the ubiquitination and disassembly of more replisomes. This model has important implications for the mechanism of action of cancer therapies that induce the untimely activation of CDK1, thereby triggering premature replisome disassembly and DNA damage.
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