Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion

Chromatin assembly and the establishment of sister chromatid cohesion are intimately connected to the progression of DNA replication forks. Here we examined the genetic interaction between the heterotrimeric chromatin assembly factor-1 (CAF-1), a central component of chromatin assembly during replic...

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Главные авторы: Nagham Ghaddar, Pierre Luciano, Vincent Géli, Yves Corda
Формат: Статья
Язык:English
Опубликовано: Shared Science Publishers OG 2023-08-01
Серии:Cell Stress
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Online-ссылка:http://www.cell-stress.com/researcharticles/2023a-ghaddar-cell-stress/
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author Nagham Ghaddar
Pierre Luciano
Vincent Géli
Yves Corda
author_facet Nagham Ghaddar
Pierre Luciano
Vincent Géli
Yves Corda
author_sort Nagham Ghaddar
collection DOAJ
description Chromatin assembly and the establishment of sister chromatid cohesion are intimately connected to the progression of DNA replication forks. Here we examined the genetic interaction between the heterotrimeric chromatin assembly factor-1 (CAF-1), a central component of chromatin assembly during replication, and the core replisome component Ctf4. We find that CAF-1 deficient cells as well as cells affected in newly-synthesized H3-H4 histones deposition during DNA rep-lication exhibit a severe negative growth with ctf4∆ mutant. We dissected the role of CAF-1 in the maintenance of genome stability in ctf4∆ yeast cells. In the absence of CTF4, CAF-1 is essential for viability in cells experiencing replication problems, in cells lacking functional S-phase checkpoint or functional spindle checkpoint, and in cells lacking DNA repair pathways involving homologous recombination. We present evidence that CAF-1 affects cohesin association to chromatin in a DNA-damage-dependent manner and is essential to maintain cohesion in the absence of CTF4. We also show that Eco1-catalyzed Smc3 acetylation is reduced in absence of CAF-1. Furthermore, we describe genetic interactions between CAF-1 and essential genes involved in cohesin loading, cohesin stabilization, and cohesin component indicating that CAF-1 is crucial for viability when sister chromatid cohesion is affected. Finally, our data indicate that the CAF-1-dependent pathway required for cohesion is functionally distinct from the Rtt101-Mms1-Mms22 pathway which functions in replicated chromatin assembly. Collectively, our results suggest that the deposition by CAF-1 of newly-synthesized H3-H4 histones during DNA replication creates a chromatin environment that favors sister chromatid cohesion and maintains genome integrity.
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spelling doaj.art-e6d85848aee64a62b9c2367b8d1f279f2023-08-20T18:50:52ZengShared Science Publishers OGCell Stress2523-02042023-08-0179698910.15698/cst2023.09.289Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesionNagham Ghaddar0Pierre Luciano1Vincent Géli2Yves Corda3Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix Marseille Univ, Institut Paoli-Calmettes, Marseille, France. Ligue Nationale Contre le Cancer (Labeled Equip).Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix Marseille Univ, Institut Paoli-Calmettes, Marseille, France. Ligue Nationale Contre le Cancer (Labeled Equip).Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix Marseille Univ, Institut Paoli-Calmettes, Marseille, France. Ligue Nationale Contre le Cancer (Labeled Equip).Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix Marseille Univ, Institut Paoli-Calmettes, Marseille, France. Ligue Nationale Contre le Cancer (Labeled Equip).Chromatin assembly and the establishment of sister chromatid cohesion are intimately connected to the progression of DNA replication forks. Here we examined the genetic interaction between the heterotrimeric chromatin assembly factor-1 (CAF-1), a central component of chromatin assembly during replication, and the core replisome component Ctf4. We find that CAF-1 deficient cells as well as cells affected in newly-synthesized H3-H4 histones deposition during DNA rep-lication exhibit a severe negative growth with ctf4∆ mutant. We dissected the role of CAF-1 in the maintenance of genome stability in ctf4∆ yeast cells. In the absence of CTF4, CAF-1 is essential for viability in cells experiencing replication problems, in cells lacking functional S-phase checkpoint or functional spindle checkpoint, and in cells lacking DNA repair pathways involving homologous recombination. We present evidence that CAF-1 affects cohesin association to chromatin in a DNA-damage-dependent manner and is essential to maintain cohesion in the absence of CTF4. We also show that Eco1-catalyzed Smc3 acetylation is reduced in absence of CAF-1. Furthermore, we describe genetic interactions between CAF-1 and essential genes involved in cohesin loading, cohesin stabilization, and cohesin component indicating that CAF-1 is crucial for viability when sister chromatid cohesion is affected. Finally, our data indicate that the CAF-1-dependent pathway required for cohesion is functionally distinct from the Rtt101-Mms1-Mms22 pathway which functions in replicated chromatin assembly. Collectively, our results suggest that the deposition by CAF-1 of newly-synthesized H3-H4 histones during DNA replication creates a chromatin environment that favors sister chromatid cohesion and maintains genome integrity.http://www.cell-stress.com/researcharticles/2023a-ghaddar-cell-stress/caf-1ctf4replicationchromatin assemblysister chromatid cohesion
spellingShingle Nagham Ghaddar
Pierre Luciano
Vincent Géli
Yves Corda
Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion
Cell Stress
caf-1
ctf4
replication
chromatin assembly
sister chromatid cohesion
title Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion
title_full Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion
title_fullStr Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion
title_full_unstemmed Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion
title_short Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion
title_sort chromatin assembly factor 1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion
topic caf-1
ctf4
replication
chromatin assembly
sister chromatid cohesion
url http://www.cell-stress.com/researcharticles/2023a-ghaddar-cell-stress/
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AT pierreluciano chromatinassemblyfactor1preservesgenomestabilityinctf4cellsbypromotingsisterchromatidcohesion
AT vincentgeli chromatinassemblyfactor1preservesgenomestabilityinctf4cellsbypromotingsisterchromatidcohesion
AT yvescorda chromatinassemblyfactor1preservesgenomestabilityinctf4cellsbypromotingsisterchromatidcohesion