Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability

All organisms depend on the ability of cells to accurately duplicate and segregate DNA into progeny. However, DNA is frequently damaged by factors in the environment and from within cells. One of the most dangerous lesions is a DNA double-strand break. Unrepaired breaks are a major driving force for...

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Autores principales: Brandon J. Payliss, Ayushi Patel, Anneka C. Sheppard, Haley D. M. Wyatt
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/f2f19c7c5e4f4094a492af45ec813ef0
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spelling oai:doaj.org-article:f2f19c7c5e4f4094a492af45ec813ef02021-11-04T06:43:11ZExploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability1664-802110.3389/fgene.2021.784167https://doaj.org/article/f2f19c7c5e4f4094a492af45ec813ef02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.784167/fullhttps://doaj.org/toc/1664-8021All organisms depend on the ability of cells to accurately duplicate and segregate DNA into progeny. However, DNA is frequently damaged by factors in the environment and from within cells. One of the most dangerous lesions is a DNA double-strand break. Unrepaired breaks are a major driving force for genome instability. Cells contain sophisticated DNA repair networks to counteract the harmful effects of genotoxic agents, thus safeguarding genome integrity. Homologous recombination is a high-fidelity, template-dependent DNA repair pathway essential for the accurate repair of DNA nicks, gaps and double-strand breaks. Accurate homologous recombination depends on the ability of cells to remove branched DNA structures that form during repair, which is achieved through the opposing actions of helicases and structure-selective endonucleases. This review focuses on a structure-selective endonuclease called SLX1-SLX4 and the macromolecular endonuclease complexes that assemble on the SLX4 scaffold. First, we discuss recent developments that illuminate the structure and biochemical properties of this somewhat atypical structure-selective endonuclease. We then summarize the multifaceted roles that are fulfilled by human SLX1-SLX4 and its associated endonucleases in homologous recombination and genome stability. Finally, we discuss recent work on SLX4-binding proteins that may represent integral components of these macromolecular nuclease complexes, emphasizing the structure and function of a protein called SLX4IP.Brandon J. PaylissAyushi PatelAnneka C. SheppardHaley D. M. WyattHaley D. M. WyattFrontiers Media S.A.articleSLX1-SLX4MUS81-EME1XPF-ERCC1SLX4IPstructure-selective endonucleasehomologous recombination (HR)GeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic SLX1-SLX4
MUS81-EME1
XPF-ERCC1
SLX4IP
structure-selective endonuclease
homologous recombination (HR)
Genetics
QH426-470
spellingShingle SLX1-SLX4
MUS81-EME1
XPF-ERCC1
SLX4IP
structure-selective endonuclease
homologous recombination (HR)
Genetics
QH426-470
Brandon J. Payliss
Ayushi Patel
Anneka C. Sheppard
Haley D. M. Wyatt
Haley D. M. Wyatt
Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability
description All organisms depend on the ability of cells to accurately duplicate and segregate DNA into progeny. However, DNA is frequently damaged by factors in the environment and from within cells. One of the most dangerous lesions is a DNA double-strand break. Unrepaired breaks are a major driving force for genome instability. Cells contain sophisticated DNA repair networks to counteract the harmful effects of genotoxic agents, thus safeguarding genome integrity. Homologous recombination is a high-fidelity, template-dependent DNA repair pathway essential for the accurate repair of DNA nicks, gaps and double-strand breaks. Accurate homologous recombination depends on the ability of cells to remove branched DNA structures that form during repair, which is achieved through the opposing actions of helicases and structure-selective endonucleases. This review focuses on a structure-selective endonuclease called SLX1-SLX4 and the macromolecular endonuclease complexes that assemble on the SLX4 scaffold. First, we discuss recent developments that illuminate the structure and biochemical properties of this somewhat atypical structure-selective endonuclease. We then summarize the multifaceted roles that are fulfilled by human SLX1-SLX4 and its associated endonucleases in homologous recombination and genome stability. Finally, we discuss recent work on SLX4-binding proteins that may represent integral components of these macromolecular nuclease complexes, emphasizing the structure and function of a protein called SLX4IP.
format article
author Brandon J. Payliss
Ayushi Patel
Anneka C. Sheppard
Haley D. M. Wyatt
Haley D. M. Wyatt
author_facet Brandon J. Payliss
Ayushi Patel
Anneka C. Sheppard
Haley D. M. Wyatt
Haley D. M. Wyatt
author_sort Brandon J. Payliss
title Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability
title_short Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability
title_full Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability
title_fullStr Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability
title_full_unstemmed Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability
title_sort exploring the structures and functions of macromolecular slx4-nuclease complexes in genome stability
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/f2f19c7c5e4f4094a492af45ec813ef0
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