Structure and function of the Asf1 histone chaperone.
Carl Mann, Jean-Yves Thuret, Raphaël Guerois, Florence Mousson, Francoise Ochsenbein
SBGM and SBFM, CEA/Saclay, Bat. 144, Gif-sur-Yvette, 91191, France
Asf1 is a histone chaperone that has been implicated in nucleosome assembly, in the cellular response to DNA damage, and in transcriptional silencing. Multiple binding partners of Asf1 have been described, including the histone H3, the Hir and CAF-I histone chaperones, the SAS-I histone acetyltransferase complex, TAF-associated bromodomains, the Brahma ATPase, and the Rad53 and Tlk protein kinases. We have determined the NMR solution structure of the highly conserved and functional N-terminal domain of the human Asf1a isoform. This domain adopts an immunoglobulin-like fold that can form a complex with the histones H3 and H4. The addition of a histone H3 peptide perturbs the chemical shift of residues forming a localized surface on Asf1. Several of these residues have been mutated in the budding yeast homolog of Asf1, and the effect of these mutations on the various Asf1 functions will be presented and contrasted with mutations that affect the binding of the Hir proteins.
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