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DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci

DNA double strand breaks (DSBs) pose a high risk for genome integrity. Cells repair DSBs through homologous recombination (HR) when a sister chromatid is available. HR is upregulated by the cycling dependent kinase (CDK) despite the paradox of telophase, where CDK is high but a sister chromatid is n...

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Autores principales: Ayra-Plasencia, Jessel, Machín, Félix
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598993/
https://www.ncbi.nlm.nih.gov/pubmed/31253793
http://dx.doi.org/10.1038/s41467-019-10742-8
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author Ayra-Plasencia, Jessel
Machín, Félix
author_facet Ayra-Plasencia, Jessel
Machín, Félix
author_sort Ayra-Plasencia, Jessel
collection PubMed
description DNA double strand breaks (DSBs) pose a high risk for genome integrity. Cells repair DSBs through homologous recombination (HR) when a sister chromatid is available. HR is upregulated by the cycling dependent kinase (CDK) despite the paradox of telophase, where CDK is high but a sister chromatid is not nearby. Here we study in the budding yeast the response to DSBs in telophase, and find they activate the DNA damage checkpoint (DDC), leading to a telophase-to-G(1) delay. Outstandingly, we observe a partial reversion of sister chromatid segregation, which includes approximation of segregated material, de novo formation of anaphase bridges, and coalescence between sister loci. We finally show that DSBs promote a massive change in the dynamics of telophase microtubules (MTs), together with dephosphorylation and relocalization of kinesin-5 Cin8. We propose that chromosome segregation is not irreversible and that DSB repair using the sister chromatid is possible in telophase.
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spelling pubmed-65989932019-07-01 DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci Ayra-Plasencia, Jessel Machín, Félix Nat Commun Article DNA double strand breaks (DSBs) pose a high risk for genome integrity. Cells repair DSBs through homologous recombination (HR) when a sister chromatid is available. HR is upregulated by the cycling dependent kinase (CDK) despite the paradox of telophase, where CDK is high but a sister chromatid is not nearby. Here we study in the budding yeast the response to DSBs in telophase, and find they activate the DNA damage checkpoint (DDC), leading to a telophase-to-G(1) delay. Outstandingly, we observe a partial reversion of sister chromatid segregation, which includes approximation of segregated material, de novo formation of anaphase bridges, and coalescence between sister loci. We finally show that DSBs promote a massive change in the dynamics of telophase microtubules (MTs), together with dephosphorylation and relocalization of kinesin-5 Cin8. We propose that chromosome segregation is not irreversible and that DSB repair using the sister chromatid is possible in telophase. Nature Publishing Group UK 2019-06-28 /pmc/articles/PMC6598993/ /pubmed/31253793 http://dx.doi.org/10.1038/s41467-019-10742-8 Text en © The Author(s) 2019 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/.
spellingShingle Article
Ayra-Plasencia, Jessel
Machín, Félix
DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
title DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
title_full DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
title_fullStr DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
title_full_unstemmed DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
title_short DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
title_sort dna double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598993/
https://www.ncbi.nlm.nih.gov/pubmed/31253793
http://dx.doi.org/10.1038/s41467-019-10742-8
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