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The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops

Homologous recombination (HR) is a ubiquitous and efficient process that serves the repair of severe forms of DNA damage and the generation of genetic diversity during meiosis. HR can proceed via multiple pathways with different outcomes that may aid or impair genome stability and faithful inheritan...

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Autores principales: Harami, Gábor M., Pálinkás, János, Seol, Yeonee, Kovács, Zoltán J., Gyimesi, Máté, Harami-Papp, Hajnalka, Neuman, Keir C., Kovács, Mihály
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813930/
https://www.ncbi.nlm.nih.gov/pubmed/35115525
http://dx.doi.org/10.1038/s41467-022-28208-9
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author Harami, Gábor M.
Pálinkás, János
Seol, Yeonee
Kovács, Zoltán J.
Gyimesi, Máté
Harami-Papp, Hajnalka
Neuman, Keir C.
Kovács, Mihály
author_facet Harami, Gábor M.
Pálinkás, János
Seol, Yeonee
Kovács, Zoltán J.
Gyimesi, Máté
Harami-Papp, Hajnalka
Neuman, Keir C.
Kovács, Mihály
author_sort Harami, Gábor M.
collection PubMed
description Homologous recombination (HR) is a ubiquitous and efficient process that serves the repair of severe forms of DNA damage and the generation of genetic diversity during meiosis. HR can proceed via multiple pathways with different outcomes that may aid or impair genome stability and faithful inheritance, underscoring the importance of HR quality control. Human Bloom’s syndrome (BLM, RecQ family) helicase plays central roles in HR pathway selection and quality control via unexplored molecular mechanisms. Here we show that BLM’s multi-domain structural architecture supports a balance between stabilization and disruption of displacement loops (D-loops), early HR intermediates that are key targets for HR regulation. We find that this balance is markedly shifted toward efficient D-loop disruption by the presence of BLM’s interaction partners Topoisomerase IIIα-RMI1-RMI2, which have been shown to be involved in multiple steps of HR-based DNA repair. Our results point to a mechanism whereby BLM can differentially process D-loops and support HR control depending on cellular regulatory mechanisms.
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spelling pubmed-88139302022-02-10 The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops Harami, Gábor M. Pálinkás, János Seol, Yeonee Kovács, Zoltán J. Gyimesi, Máté Harami-Papp, Hajnalka Neuman, Keir C. Kovács, Mihály Nat Commun Article Homologous recombination (HR) is a ubiquitous and efficient process that serves the repair of severe forms of DNA damage and the generation of genetic diversity during meiosis. HR can proceed via multiple pathways with different outcomes that may aid or impair genome stability and faithful inheritance, underscoring the importance of HR quality control. Human Bloom’s syndrome (BLM, RecQ family) helicase plays central roles in HR pathway selection and quality control via unexplored molecular mechanisms. Here we show that BLM’s multi-domain structural architecture supports a balance between stabilization and disruption of displacement loops (D-loops), early HR intermediates that are key targets for HR regulation. We find that this balance is markedly shifted toward efficient D-loop disruption by the presence of BLM’s interaction partners Topoisomerase IIIα-RMI1-RMI2, which have been shown to be involved in multiple steps of HR-based DNA repair. Our results point to a mechanism whereby BLM can differentially process D-loops and support HR control depending on cellular regulatory mechanisms. Nature Publishing Group UK 2022-02-03 /pmc/articles/PMC8813930/ /pubmed/35115525 http://dx.doi.org/10.1038/s41467-022-28208-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Harami, Gábor M.
Pálinkás, János
Seol, Yeonee
Kovács, Zoltán J.
Gyimesi, Máté
Harami-Papp, Hajnalka
Neuman, Keir C.
Kovács, Mihály
The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops
title The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops
title_full The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops
title_fullStr The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops
title_full_unstemmed The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops
title_short The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops
title_sort toposiomerase iiialpha-rmi1-rmi2 complex orients human bloom’s syndrome helicase for efficient disruption of d-loops
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813930/
https://www.ncbi.nlm.nih.gov/pubmed/35115525
http://dx.doi.org/10.1038/s41467-022-28208-9
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