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标题：Structural basis for the interaction of Asf1 with histone H3 and its functional implications
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作者：Florence Mousson ; Aurélie Lautrette ; Jean-Yves Thuret 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：17
页码：5975-5980
DOI：10.1073/pnas.0500149102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：Asf1 histone chaperone ; chromatin ; DNA damage ; NMR chemical shift mapping ; nucleosome assembly