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Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe
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Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe
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Journal Article
Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe
2024
Overview
Genome and epigenome integrity in eukaryotes depends on the proper coupling of histone deposition with DNA synthesis. This process relies on the evolutionary conserved histone chaperone CAF-1 for which the links between structure and functions are still a puzzle. While studies of the Saccharomyces cerevisiae CAF-1 complex enabled to propose a model for the histone deposition mechanism, we still lack a framework to demonstrate its generality and in particular, how its interaction with the polymerase accessory factor PCNA is operating. Here, we reconstituted a complete Sp CAF-1 from fission yeast. We characterized its dynamic structure using NMR, SAXS and molecular modeling together with in vitro and in vivo functional studies on rationally designed interaction mutants. Importantly, we identify the unfolded nature of the acidic domain which folds up when binding to histones. We also show how the long KER helix mediates DNA binding and stimulates Sp CAF-1 association with PCNA. Our study highlights how the organization of CAF-1 comprising both disordered regions and folded modules enables the dynamics of multiple interactions to promote synthesis-coupled histone deposition essential for its DNA replication, heterochromatin maintenance, and genome stability functions.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publication
Subject
Biochemistry, Molecular Biology
/ Cartoons
/ DNA
/ Genomes
/ Genomics
/ Histones
/ Microbiology and Parasitology
/ Mycology
/ nmr
/ Proliferating cell nuclear antigen
/ Proliferating Cell Nuclear Antigen - genetics
/ Proliferating Cell Nuclear Antigen - metabolism
/ Saccharomyces cerevisiae - genetics
/ saxs
/ Schizosaccharomyces - genetics
/ Schizosaccharomyces - metabolism
/ Software
/ Yeast
