Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe
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 c...
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eLife Sciences Publications Ltd
2024-02-01
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| Online Access: | https://elifesciences.org/articles/91461 |
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| author | Fouad Ouasti Maxime Audin Karine Fréon Jean-Pierre Quivy Mehdi Tachekort Elizabeth Cesard Aurélien Thureau Virginie Ropars Paloma Fernández Varela Gwenaelle Moal Ibrahim Soumana Adamou Aleksandra Uryga Pierre Legrand Jessica Andreani Raphaël Guerois Geneviève Almouzni Sarah Lambert Francoise Ochsenbein |
| author_facet | Fouad Ouasti Maxime Audin Karine Fréon Jean-Pierre Quivy Mehdi Tachekort Elizabeth Cesard Aurélien Thureau Virginie Ropars Paloma Fernández Varela Gwenaelle Moal Ibrahim Soumana Adamou Aleksandra Uryga Pierre Legrand Jessica Andreani Raphaël Guerois Geneviève Almouzni Sarah Lambert Francoise Ochsenbein |
| author_sort | Fouad Ouasti |
| collection | DOAJ |
| description | 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 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 synthesis-coupled histone deposition essential for its DNA replication, heterochromatin maintenance, and genome stability functions. |
| format | Article |
| id | doaj-art-e4eaadc73ce04cfaa4c47752fee0fda9 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-e4eaadc73ce04cfaa4c47752fee0fda92025-08-20T02:26:20ZengeLife Sciences Publications LtdeLife2050-084X2024-02-011210.7554/eLife.91461Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombeFouad Ouasti0Maxime Audin1Karine Fréon2https://orcid.org/0000-0001-7853-078XJean-Pierre Quivy3https://orcid.org/0000-0001-6557-7204Mehdi Tachekort4Elizabeth Cesard5Aurélien Thureau6Virginie Ropars7Paloma Fernández Varela8Gwenaelle Moal9Ibrahim Soumana Adamou10Aleksandra Uryga11Pierre Legrand12Jessica Andreani13https://orcid.org/0000-0003-4435-9093Raphaël Guerois14https://orcid.org/0000-0001-5294-2858Geneviève Almouzni15Sarah Lambert16https://orcid.org/0000-0002-1403-3204Francoise Ochsenbein17https://orcid.org/0000-0002-9027-4384Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceInstitut Curie, PSL Research University, CNRS UMR 3348, INSERM U1278, Université Paris-Saclay, Equipe labellisée Ligue contre le Cancer, Orsay, FranceInstitut Curie, PSL Research University, CNRS, Sorbonne Université,CNRS UMR3664, Nuclear Dynamics Unit, Équipe Labellisée Ligue contre le Cancer, Paris, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceSynchrotron SOLEIL, HelioBio group, l'Orme des Merisiers, Saint-Aubin, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceInstitut Curie, PSL Research University, CNRS UMR 3348, INSERM U1278, Université Paris-Saclay, Equipe labellisée Ligue contre le Cancer, Orsay, FranceInstitut Curie, PSL Research University, CNRS UMR 3348, INSERM U1278, Université Paris-Saclay, Equipe labellisée Ligue contre le Cancer, Orsay, FranceSynchrotron SOLEIL, HelioBio group, l'Orme des Merisiers, Saint-Aubin, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceInstitut Curie, PSL Research University, CNRS, Sorbonne Université,CNRS UMR3664, Nuclear Dynamics Unit, Équipe Labellisée Ligue contre le Cancer, Paris, FranceInstitut Curie, PSL Research University, CNRS UMR 3348, INSERM U1278, Université Paris-Saclay, Equipe labellisée Ligue contre le Cancer, Orsay, FranceUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, Gif-sur-Yvette, FranceGenome 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 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 synthesis-coupled histone deposition essential for its DNA replication, heterochromatin maintenance, and genome stability functions.https://elifesciences.org/articles/91461histone chaperoneNucleosome assemblyepigeneticgenome integritynmrsaxs |
| spellingShingle | Fouad Ouasti Maxime Audin Karine Fréon Jean-Pierre Quivy Mehdi Tachekort Elizabeth Cesard Aurélien Thureau Virginie Ropars Paloma Fernández Varela Gwenaelle Moal Ibrahim Soumana Adamou Aleksandra Uryga Pierre Legrand Jessica Andreani Raphaël Guerois Geneviève Almouzni Sarah Lambert Francoise Ochsenbein Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe eLife histone chaperone Nucleosome assembly epigenetic genome integrity nmr saxs |
| title | Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe |
| title_full | Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe |
| title_fullStr | Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe |
| title_full_unstemmed | Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe |
| title_short | Disordered regions and folded modules in CAF-1 promote histone deposition in Schizosaccharomyces pombe |
| title_sort | disordered regions and folded modules in caf 1 promote histone deposition in schizosaccharomyces pombe |
| topic | histone chaperone Nucleosome assembly epigenetic genome integrity nmr saxs |
| url | https://elifesciences.org/articles/91461 |
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