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Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors

Functional telomeres in yeast lacking telomerase can be restored by rare Rad51- or Rad59-dependent recombination events that lead to type I and type II survivors, respectively. We previously proposed that polySUMOylation of proteins and the SUMO-targeted ubiquitin ligase Slx5-Slx8 are key factors in...

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Autores principales: Charifi, Ferose, Churikov, Dmitri, Eckert-Boulet, Nadine, Minguet, Christopher, Jourquin, Frédéric, Hardy, Julien, Lisby, Michael, Simon, Marie-Noëlle, Géli, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966982/
https://www.ncbi.nlm.nih.gov/pubmed/33748714
http://dx.doi.org/10.1016/j.isci.2021.102231
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author Charifi, Ferose
Churikov, Dmitri
Eckert-Boulet, Nadine
Minguet, Christopher
Jourquin, Frédéric
Hardy, Julien
Lisby, Michael
Simon, Marie-Noëlle
Géli, Vincent
author_facet Charifi, Ferose
Churikov, Dmitri
Eckert-Boulet, Nadine
Minguet, Christopher
Jourquin, Frédéric
Hardy, Julien
Lisby, Michael
Simon, Marie-Noëlle
Géli, Vincent
author_sort Charifi, Ferose
collection PubMed
description Functional telomeres in yeast lacking telomerase can be restored by rare Rad51- or Rad59-dependent recombination events that lead to type I and type II survivors, respectively. We previously proposed that polySUMOylation of proteins and the SUMO-targeted ubiquitin ligase Slx5-Slx8 are key factors in type II recombination. Here, we show that SUMOylation of Rad52 favors the formation of type I survivors. Conversely, preventing Rad52 SUMOylation partially bypasses the requirement of Slx5-Slx8 for type II recombination. We further report that SUMO-dependent proteasomal degradation favors type II recombination. Finally, inactivation of Rad59, but not Rad51, impairs the relocation of eroded telomeres to the Nuclear Pore complexes (NPCs). We propose that Rad59 cooperates with non-SUMOylated Rad52 to promote type II recombination at NPCs, resulting in the emergence of more robust survivors akin to ALT cancer cells. Finally, neither Rad59 nor Rad51 is required by itself for the survival of established type II survivors.
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spelling pubmed-79669822021-03-19 Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors Charifi, Ferose Churikov, Dmitri Eckert-Boulet, Nadine Minguet, Christopher Jourquin, Frédéric Hardy, Julien Lisby, Michael Simon, Marie-Noëlle Géli, Vincent iScience Article Functional telomeres in yeast lacking telomerase can be restored by rare Rad51- or Rad59-dependent recombination events that lead to type I and type II survivors, respectively. We previously proposed that polySUMOylation of proteins and the SUMO-targeted ubiquitin ligase Slx5-Slx8 are key factors in type II recombination. Here, we show that SUMOylation of Rad52 favors the formation of type I survivors. Conversely, preventing Rad52 SUMOylation partially bypasses the requirement of Slx5-Slx8 for type II recombination. We further report that SUMO-dependent proteasomal degradation favors type II recombination. Finally, inactivation of Rad59, but not Rad51, impairs the relocation of eroded telomeres to the Nuclear Pore complexes (NPCs). We propose that Rad59 cooperates with non-SUMOylated Rad52 to promote type II recombination at NPCs, resulting in the emergence of more robust survivors akin to ALT cancer cells. Finally, neither Rad59 nor Rad51 is required by itself for the survival of established type II survivors. Elsevier 2021-02-25 /pmc/articles/PMC7966982/ /pubmed/33748714 http://dx.doi.org/10.1016/j.isci.2021.102231 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Charifi, Ferose
Churikov, Dmitri
Eckert-Boulet, Nadine
Minguet, Christopher
Jourquin, Frédéric
Hardy, Julien
Lisby, Michael
Simon, Marie-Noëlle
Géli, Vincent
Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors
title Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors
title_full Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors
title_fullStr Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors
title_full_unstemmed Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors
title_short Rad52 SUMOylation functions as a molecular switch that determines a balance between the Rad51- and Rad59-dependent survivors
title_sort rad52 sumoylation functions as a molecular switch that determines a balance between the rad51- and rad59-dependent survivors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966982/
https://www.ncbi.nlm.nih.gov/pubmed/33748714
http://dx.doi.org/10.1016/j.isci.2021.102231
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