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Structural basis for the interaction of Asf1 with histone H3 and its functional implications

Florence Mousson 1 Aurélie Lautrette 1 Jean-Yves Thuret 2 Morgane Agez 3, 1 Régis Courbeyrette 2 Béatrice Amigues 4, 1 Emmanuelle Becker 1 Jean-Michel Neumann 1 Raphael Guérois 1 Carl Mann 5, * Françoise Ochsenbein 1, *
* Corresponding author
1 Service de Biophysique des Fonctions Membranaires
2 IBITECS - Institut de Biologie et de Technologies de Saclay
3 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
4 Institut Curie [Paris]
5 Service de Biochimie et Génétique Moléculaire, CEA/Saclay
Abstract : Asf1 is a conserved histone chaperone implicated in nucleosome assembly, transcriptional silencing, and the cellular response to DNA damage. We solved the NMR solution structure of the N-terminal functional domain of the human Asf1a isoform, and we identified by NMR chemical shift mapping a surface of Asf1a that binds the C-terminal helix of histone H3. This binding surface forms a highly conserved hydrophobic groove surrounded by charged residues. Mutations within this binding site decreased the affinity of Asf1a for the histone H3/H4 complex in vitro, and the same mutations in the homologous yeast protein led to transcriptional silencing defects, DNA damage sensitivity, and thermosensitive growth. We have thus obtained direct experimental evidence of the mode of binding between a histone and one of its chaperones and genetic data suggesting that this interaction is important in both the DNA damage response and transcriptional silencing.
Keywords : Asf1 histone chaperone chromatin DNA damage NMR chemical shift mapping nucleosome assembly
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https://hal-cea.archives-ouvertes.fr/cea-01744427
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Submitted on : Tuesday, March 27, 2018 - 1:40:39 PM
Last modification on : Monday, December 13, 2021 - 9:14:58 AM

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Florence Mousson, Aurélie Lautrette, Jean-Yves Thuret, Morgane Agez, Régis Courbeyrette, et al.. Structural basis for the interaction of Asf1 with histone H3 and its functional implications. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2005, 102, pp.5975 - 5980. ⟨10.1073/pnas.0500149102⟩. ⟨cea-01744427⟩

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