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The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks

DNA damage tolerance (DDT) is crucial for genome integrity maintenance. DDT is mainly carried out by template switch recombination, an error-free mode of overcoming DNA lesions, or translesion DNA synthesis, which is error-prone. Here, we investigated the role of Mgs1/WRNIP1 in modulating DDT. Using...

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Autores principales: Jiménez-Martín, Alberto, Saugar, Irene, Joseph, Chinnu Rose, Mayer, Alexandra, Lehmann, Carl P., Szakal, Barnabas, Branzei, Dana, Tercero, José Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141828/
https://www.ncbi.nlm.nih.gov/pubmed/32285001
http://dx.doi.org/10.1126/sciadv.aaz3327
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author Jiménez-Martín, Alberto
Saugar, Irene
Joseph, Chinnu Rose
Mayer, Alexandra
Lehmann, Carl P.
Szakal, Barnabas
Branzei, Dana
Tercero, José Antonio
author_facet Jiménez-Martín, Alberto
Saugar, Irene
Joseph, Chinnu Rose
Mayer, Alexandra
Lehmann, Carl P.
Szakal, Barnabas
Branzei, Dana
Tercero, José Antonio
author_sort Jiménez-Martín, Alberto
collection PubMed
description DNA damage tolerance (DDT) is crucial for genome integrity maintenance. DDT is mainly carried out by template switch recombination, an error-free mode of overcoming DNA lesions, or translesion DNA synthesis, which is error-prone. Here, we investigated the role of Mgs1/WRNIP1 in modulating DDT. Using budding yeast, we found that elimination of Mgs1 in cells lacking Rad5, an essential protein for DDT, activates an alternative mode of DNA damage bypass, driven by recombination, which allows chromosome replication and cell viability under stress conditions that block DNA replication forks. This salvage pathway is RAD52 and RAD59 dependent, requires the DNA polymerase δ and PCNA modification at K164, and is enabled by Esc2 and the PCNA unloader Elg1, being inhibited when Mgs1 is present. We propose that Mgs1 is necessary to prevent a potentially toxic recombination salvage pathway at sites of perturbed replication, which, in turn, favors Rad5-dependent template switching, thus helping to preserve genome stability.
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spelling pubmed-71418282020-04-13 The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks Jiménez-Martín, Alberto Saugar, Irene Joseph, Chinnu Rose Mayer, Alexandra Lehmann, Carl P. Szakal, Barnabas Branzei, Dana Tercero, José Antonio Sci Adv Research Articles DNA damage tolerance (DDT) is crucial for genome integrity maintenance. DDT is mainly carried out by template switch recombination, an error-free mode of overcoming DNA lesions, or translesion DNA synthesis, which is error-prone. Here, we investigated the role of Mgs1/WRNIP1 in modulating DDT. Using budding yeast, we found that elimination of Mgs1 in cells lacking Rad5, an essential protein for DDT, activates an alternative mode of DNA damage bypass, driven by recombination, which allows chromosome replication and cell viability under stress conditions that block DNA replication forks. This salvage pathway is RAD52 and RAD59 dependent, requires the DNA polymerase δ and PCNA modification at K164, and is enabled by Esc2 and the PCNA unloader Elg1, being inhibited when Mgs1 is present. We propose that Mgs1 is necessary to prevent a potentially toxic recombination salvage pathway at sites of perturbed replication, which, in turn, favors Rad5-dependent template switching, thus helping to preserve genome stability. American Association for the Advancement of Science 2020-04-08 /pmc/articles/PMC7141828/ /pubmed/32285001 http://dx.doi.org/10.1126/sciadv.aaz3327 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Jiménez-Martín, Alberto
Saugar, Irene
Joseph, Chinnu Rose
Mayer, Alexandra
Lehmann, Carl P.
Szakal, Barnabas
Branzei, Dana
Tercero, José Antonio
The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks
title The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks
title_full The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks
title_fullStr The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks
title_full_unstemmed The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks
title_short The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks
title_sort mgs1/wrnip1 atpase is required to prevent a recombination salvage pathway at damaged replication forks
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141828/
https://www.ncbi.nlm.nih.gov/pubmed/32285001
http://dx.doi.org/10.1126/sciadv.aaz3327
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