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Genes 2019, 10(3), 232; https://doi.org/10.3390/genes10030232

Structure-Specific Endonucleases and the Resolution of Chromosome Underreplication

1
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland
2
Faculty of Natural Sciences, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland
3
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK
*
Author to whom correspondence should be addressed.
Received: 22 February 2019 / Revised: 11 March 2019 / Accepted: 13 March 2019 / Published: 19 March 2019
(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)
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Abstract

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. View Full-Text
Keywords: DNA replication; chromosome stability; replication stress; Holliday junction resolvase; structure-specific nuclease; ultrafine anaphase bridge; chromosome segregation; mitotic DNA synthesis; genome stability DNA replication; chromosome stability; replication stress; Holliday junction resolvase; structure-specific nuclease; ultrafine anaphase bridge; chromosome segregation; mitotic DNA synthesis; genome stability
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Falquet, B.; Rass, U. Structure-Specific Endonucleases and the Resolution of Chromosome Underreplication. Genes 2019, 10, 232.

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