Structure-specific endonucleases and the resolution of chromosome underreplication

Falquet, Benoît and Rass, Ulrich (2019) Structure-specific endonucleases and the resolution of chromosome underreplication. Genes, 10 (3). p. 232. ISSN 2073-4425

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Complete genome duplication in every cell cycle is fundamental for genome stability and cell survival. However, chromosome replication is frequently challenged by obstacles that impede DNA replication fork (RF) progression, which subsequently causes replication stress (RS). Cells have evolved pathways of RF protection and restart that mitigate the consequences of RS and promote the completion of DNA synthesis prior to mitotic chromosome segregation. If there is entry into mitosis with underreplicated chromosomes, this results in sister-chromatid entanglements, chromosome breakage and rearrangements and aneuploidy in daughter cells. Here, we focus on the resolution of persistent replication intermediates by the structure-specific endonucleases (SSEs) MUS81, SLX1-SLX4 and GEN1. Their actions and a recently discovered pathway of mitotic DNA repair synthesis have emerged as important facilitators of replication completion and sister chromatid detachment in mitosis. As RS is induced by oncogene activation and is a common feature of cancer cells, any advances in our understanding of the molecular mechanisms related to chromosome underreplication have important biomedical implications.

Item Type: Article
Keywords: DNA replication, chromosome stability, replication stress, Holliday junction resolvase, structure-specific nuclease, ultrafine anaphase bridge, chromosome segregation, mitotic DNA synthesis, genome stability
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science
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Depositing User: Ulrich Rass
Date Deposited: 20 Mar 2019 08:50
Last Modified: 20 Mar 2019 08:50

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