1. Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1
- Author
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Oscar Fernandez-Capetillo, Antonio Galarreta, Emilio Lecona, Pablo Valledor, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), European Research Council, Fundación Ramón Areces, La Caixa, Consejo Superior de Investigaciones Científicas (España), and European Commission
- Subjects
CDK1 ,DNA replication initiation ,DNA damage ,DNA repair ,QH301-705.5 ,SUMO protein ,Review ,Biology ,DNA replication ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,0302 clinical medicine ,CDC2 Protein Kinase ,ubiquitin ,Animals ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,030304 developmental biology ,mitosis ,0303 health sciences ,Organic Chemistry ,General Medicine ,3. Good health ,Computer Science Applications ,Chromatin ,Cell biology ,Chemistry ,SUMO ,Small Ubiquitin-Related Modifier Proteins ,DNA replication termination ,USP7 ,Replisome ,Protein Processing, Post-Translational ,030217 neurology & neurosurgery - Abstract
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 ubiquitinmediated 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., Ramón y Cajal Fellowship from MINECO (RYC-2016-20705), co-funded by European Regional Development Funds (FEDER) to Emilio Lecona; by grants from the Spanish Ministry of Science, Innovation and Universities (RTI2018-102204-B-I00, co-financed with European FEDER funds) and the European Research Council (ERC-617840) to Oscar Fernandez-Capetillo; fellowships from Fundacion Ramon Areces-UAM and LaCaixa Foundation to Pablo Valledor (LCF/BQ/ES18/11670008)
- Published
- 2021