Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe
Year: 2023
Type: article
Abstract: 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 function are still a puzzle. While studies of the S. 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 SpCAF-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 SpCAF-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 histone deposition coupled to DNA synthesis, and is essential for CAF-1 functions in DNA replication, heterochromatin maintenance, and genome stability.
Source: eLife
Authors: Fouad Ouasti, Maxime Audin, Karine Freon, Jean-Pierre Quivy, Mehdi Tachekort, Elizabeth Cesard, Aurélien Thureau, Virginie Ropars, Paloma F. Varela, Gwenaelle Moal, Ibrahim Soumana Amadou, Aleksandra Uryga, Pierre Legrand, Jessica Andreani, Raphael Guerois, Geneviève Almouzni, Sarah Lambert, Francoise Ochsenbein
Institutions: Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris Sciences et Lettres, Université Paris-Saclay, CEA Paris-Saclay - Etablissement de Saclay, Institut de Biologie Intégrative de la Cellule, Intégrité du génome, ARN et cancer, Direction de la Recherche Fondamentale, Institut Curie, Inserm, Sorbonne Université, Dynamique du noyau, Synchrotron SOLEIL
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G1287878306, G1815747370, Structure and mechanism of replication coupled histone assembly, DNA-synthesis coupled histone assembly by the chaperone CAF-1, G293273346, G4399195447, Therapeutic targeting and chemical biology of histone chaperones using rationally designed medium-size inhibitors, Protein-Protein Interactions in Meiosis, G7240651115, Développement, Epigénèse, Epigénétique et potentiel de vie, Integrative Xer recombination complex Stabilization, Infrastructure Française pour la Biologie Structurale Intégrée
OpenAlex ID: W4387869184