Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion
Authors:Nagham Ghaddar1, Pierre Luciano1, Vincent Géli1, and Yves Corda1,*
1 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).
Keywords:
CAF-1, Ctf4, replication, chromatin assembly, sister chromatid cohesion.
Abbreviatons:
CAF-1 – chromatin assembly factor-1,
H3K56ac – Histone H3 lysine 56 acetylation,
SCC – sister chromatid cohesion,
UV – ultraviolet,
CPT – camptothecin,
HU – hydroxyurea,
MMS – methyl-methanesulfonate, WT – wild-type,
HR – homologous recombination,
γH2AX – phosphorylation of histone H2A on serine 129,
Polα – DNA-polymerase α,
ts – thermosensitive.
Corresponding Author(s):
Conflict of interest statement:
The authors declare that they have no conflict of interest.
Please cite this article as:
Nagham Ghaddar, Pierre Luciano, Vincent Géli and Yves Corda (2023). Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion. Cell Stress 7(9): 69-89. doi: 10.15698/cst2023.09.289
© 2023 Ghaddar et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
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.