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Modeling the Homologous Recombination Process: Methods, Successes and Challenges

Homologous recombination (HR) is a fundamental process common to all species. HR aims to faithfully repair DNA double strand breaks. HR involves the formation of nucleoprotein filaments on DNA single strands (ssDNA) resected from the break. The nucleoprotein filaments search for homologous regions i...

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Autores principales: Sabei, Afra, Prentiss, Mara, Prévost, Chantal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573387/
https://www.ncbi.nlm.nih.gov/pubmed/37834348
http://dx.doi.org/10.3390/ijms241914896
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author Sabei, Afra
Prentiss, Mara
Prévost, Chantal
author_facet Sabei, Afra
Prentiss, Mara
Prévost, Chantal
author_sort Sabei, Afra
collection PubMed
description Homologous recombination (HR) is a fundamental process common to all species. HR aims to faithfully repair DNA double strand breaks. HR involves the formation of nucleoprotein filaments on DNA single strands (ssDNA) resected from the break. The nucleoprotein filaments search for homologous regions in the genome and promote strand exchange with the ssDNA homologous region in an unbroken copy of the genome. HR has been the object of intensive studies for decades. Because multi-scale dynamics is a fundamental aspect of this process, studying HR is highly challenging, both experimentally and using computational approaches. Nevertheless, knowledge has built up over the years and has recently progressed at an accelerated pace, borne by increasingly focused investigations using new techniques such as single molecule approaches. Linking this knowledge to the atomic structure of the nucleoprotein filament systems and the succession of unstable, transient intermediate steps that takes place during the HR process remains a challenge; modeling retains a very strong role in bridging the gap between structures that are stable enough to be observed and in exploring transition paths between these structures. However, working on ever-changing long filament systems submitted to kinetic processes is full of pitfalls. This review presents the modeling tools that are used in such studies, their possibilities and limitations, and reviews the advances in the knowledge of the HR process that have been obtained through modeling. Notably, we will emphasize how cooperative behavior in the HR nucleoprotein filament enables modeling to produce reliable information.
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spelling pubmed-105733872023-10-14 Modeling the Homologous Recombination Process: Methods, Successes and Challenges Sabei, Afra Prentiss, Mara Prévost, Chantal Int J Mol Sci Review Homologous recombination (HR) is a fundamental process common to all species. HR aims to faithfully repair DNA double strand breaks. HR involves the formation of nucleoprotein filaments on DNA single strands (ssDNA) resected from the break. The nucleoprotein filaments search for homologous regions in the genome and promote strand exchange with the ssDNA homologous region in an unbroken copy of the genome. HR has been the object of intensive studies for decades. Because multi-scale dynamics is a fundamental aspect of this process, studying HR is highly challenging, both experimentally and using computational approaches. Nevertheless, knowledge has built up over the years and has recently progressed at an accelerated pace, borne by increasingly focused investigations using new techniques such as single molecule approaches. Linking this knowledge to the atomic structure of the nucleoprotein filament systems and the succession of unstable, transient intermediate steps that takes place during the HR process remains a challenge; modeling retains a very strong role in bridging the gap between structures that are stable enough to be observed and in exploring transition paths between these structures. However, working on ever-changing long filament systems submitted to kinetic processes is full of pitfalls. This review presents the modeling tools that are used in such studies, their possibilities and limitations, and reviews the advances in the knowledge of the HR process that have been obtained through modeling. Notably, we will emphasize how cooperative behavior in the HR nucleoprotein filament enables modeling to produce reliable information. MDPI 2023-10-04 /pmc/articles/PMC10573387/ /pubmed/37834348 http://dx.doi.org/10.3390/ijms241914896 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Sabei, Afra
Prentiss, Mara
Prévost, Chantal
Modeling the Homologous Recombination Process: Methods, Successes and Challenges
title Modeling the Homologous Recombination Process: Methods, Successes and Challenges
title_full Modeling the Homologous Recombination Process: Methods, Successes and Challenges
title_fullStr Modeling the Homologous Recombination Process: Methods, Successes and Challenges
title_full_unstemmed Modeling the Homologous Recombination Process: Methods, Successes and Challenges
title_short Modeling the Homologous Recombination Process: Methods, Successes and Challenges
title_sort modeling the homologous recombination process: methods, successes and challenges
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573387/
https://www.ncbi.nlm.nih.gov/pubmed/37834348
http://dx.doi.org/10.3390/ijms241914896
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