Table of contents

Volume 7, Issue 9, pp. 69 - 89, September 2023

Issue cover
Cover: This month in Cell Stress: Novel factors of chromatin stability. Artist's representation of DNA. Photo by Andy Leppard via, licensed under a CC BY 2.0 license. Image modified by Cell Stress. The cover is published under the CC BY 4.0 license. Enlarge issue cover

Research Articles

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

Nagham Ghaddar, Pierre Luciano, Vincent Géli and Yves Corda

page 69-89 | 10.15698/cst2023.09.289 | Full text | PDF | Abstract

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 replication 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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