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Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres
When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it i...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794921/ https://www.ncbi.nlm.nih.gov/pubmed/24130507 http://dx.doi.org/10.1371/journal.pgen.1003859 |
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author | Valerio-Santiago, Mauricio de los Santos-Velázquez, Ana Isabel Monje-Casas, Fernando |
author_facet | Valerio-Santiago, Mauricio de los Santos-Velázquez, Ana Isabel Monje-Casas, Fernando |
author_sort | Valerio-Santiago, Mauricio |
collection | PubMed |
description | When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN), in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression. |
format | Online Article Text |
id | pubmed-3794921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37949212013-10-15 Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres Valerio-Santiago, Mauricio de los Santos-Velázquez, Ana Isabel Monje-Casas, Fernando PLoS Genet Research Article When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN), in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression. Public Library of Science 2013-10-10 /pmc/articles/PMC3794921/ /pubmed/24130507 http://dx.doi.org/10.1371/journal.pgen.1003859 Text en © 2013 Valerio-Santiago et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Valerio-Santiago, Mauricio de los Santos-Velázquez, Ana Isabel Monje-Casas, Fernando Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres |
title | Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres |
title_full | Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres |
title_fullStr | Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres |
title_full_unstemmed | Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres |
title_short | Inhibition of the Mitotic Exit Network in Response to Damaged Telomeres |
title_sort | inhibition of the mitotic exit network in response to damaged telomeres |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794921/ https://www.ncbi.nlm.nih.gov/pubmed/24130507 http://dx.doi.org/10.1371/journal.pgen.1003859 |
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