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Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity
Saccharomyces cerevisiae Rad9 is required for an effective DNA damage response throughout the cell cycle. Assembly of Rad9 on chromatin after DNA damage is promoted by histone modifications that create docking sites for Rad9 recruitment, allowing checkpoint activation. Rad53 phosphorylation is also...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916856/ https://www.ncbi.nlm.nih.gov/pubmed/20700441 http://dx.doi.org/10.1371/journal.pgen.1001047 |
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author | Granata, Magda Lazzaro, Federico Novarina, Daniele Panigada, Davide Puddu, Fabio Abreu, Carla Manuela Kumar, Ramesh Grenon, Muriel Lowndes, Noel F. Plevani, Paolo Muzi-Falconi, Marco |
author_facet | Granata, Magda Lazzaro, Federico Novarina, Daniele Panigada, Davide Puddu, Fabio Abreu, Carla Manuela Kumar, Ramesh Grenon, Muriel Lowndes, Noel F. Plevani, Paolo Muzi-Falconi, Marco |
author_sort | Granata, Magda |
collection | PubMed |
description | Saccharomyces cerevisiae Rad9 is required for an effective DNA damage response throughout the cell cycle. Assembly of Rad9 on chromatin after DNA damage is promoted by histone modifications that create docking sites for Rad9 recruitment, allowing checkpoint activation. Rad53 phosphorylation is also dependent upon BRCT-directed Rad9 oligomerization; however, the crosstalk between these molecular determinants and their functional significance are poorly understood. Here we report that, in the G1 and M phases of the cell cycle, both constitutive and DNA damage-dependent Rad9 chromatin association require its BRCT domains. In G1 cells, GST or FKBP dimerization motifs can substitute to the BRCT domains for Rad9 chromatin binding and checkpoint function. Conversely, forced Rad9 dimerization in M phase fails to promote its recruitment onto DNA, although it supports Rad9 checkpoint function. In fact, a parallel pathway, independent on histone modifications and governed by CDK1 activity, allows checkpoint activation in the absence of Rad9 chromatin binding. CDK1-dependent phosphorylation of Rad9 on Ser11 leads to specific interaction with Dpb11, allowing Rad53 activation and bypassing the requirement for the histone branch. |
format | Text |
id | pubmed-2916856 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29168562010-08-10 Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity Granata, Magda Lazzaro, Federico Novarina, Daniele Panigada, Davide Puddu, Fabio Abreu, Carla Manuela Kumar, Ramesh Grenon, Muriel Lowndes, Noel F. Plevani, Paolo Muzi-Falconi, Marco PLoS Genet Research Article Saccharomyces cerevisiae Rad9 is required for an effective DNA damage response throughout the cell cycle. Assembly of Rad9 on chromatin after DNA damage is promoted by histone modifications that create docking sites for Rad9 recruitment, allowing checkpoint activation. Rad53 phosphorylation is also dependent upon BRCT-directed Rad9 oligomerization; however, the crosstalk between these molecular determinants and their functional significance are poorly understood. Here we report that, in the G1 and M phases of the cell cycle, both constitutive and DNA damage-dependent Rad9 chromatin association require its BRCT domains. In G1 cells, GST or FKBP dimerization motifs can substitute to the BRCT domains for Rad9 chromatin binding and checkpoint function. Conversely, forced Rad9 dimerization in M phase fails to promote its recruitment onto DNA, although it supports Rad9 checkpoint function. In fact, a parallel pathway, independent on histone modifications and governed by CDK1 activity, allows checkpoint activation in the absence of Rad9 chromatin binding. CDK1-dependent phosphorylation of Rad9 on Ser11 leads to specific interaction with Dpb11, allowing Rad53 activation and bypassing the requirement for the histone branch. Public Library of Science 2010-08-05 /pmc/articles/PMC2916856/ /pubmed/20700441 http://dx.doi.org/10.1371/journal.pgen.1001047 Text en Granata 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 Granata, Magda Lazzaro, Federico Novarina, Daniele Panigada, Davide Puddu, Fabio Abreu, Carla Manuela Kumar, Ramesh Grenon, Muriel Lowndes, Noel F. Plevani, Paolo Muzi-Falconi, Marco Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity |
title | Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity |
title_full | Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity |
title_fullStr | Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity |
title_full_unstemmed | Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity |
title_short | Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity |
title_sort | dynamics of rad9 chromatin binding and checkpoint function are mediated by its dimerization and are cell cycle–regulated by cdk1 activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916856/ https://www.ncbi.nlm.nih.gov/pubmed/20700441 http://dx.doi.org/10.1371/journal.pgen.1001047 |
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