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The histone chaperone Asf1 at the crossroads of chromatin and DNA checkpoint pathways

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Abstract

Nucleosome assembly involves deposition of a heterotetramer of histones H3/H4 onto DNA followed by two heterodimers of histones H2A/H2B. Cycles of nucleosome assembly and disassembly are essential to cellular events such as replication, transcription, and DNA repair. After synthesis in the cytoplasm, histones are shuttled into the nucleus where they are associated with chaperone proteins. Chaperones of histones H3/H4 include CAF-I, the Hir proteins, and Asf1. CAF-I and the Hir proteins function as replication-coupled and replication-independent deposition factors for H3/H4, respectively, whereas Asf1 may play a role in both pathways. In addition to acting as assembly factors, histone chaperones assist nucleosome dissociation from DNA and they may recruit other proteins to chromatin. The past few years have witnessed a notable accumulation of genetic, biochemical, and structural data on Asf1, which motivated this review. We discuss the sequence and structural features of Asf1 before considering its roles in nucleosome assembly/disassembly, the cellular response to DNA damage, and the regulation of gene expression. We emphasize the key role of Asf1 as a central node in a network of partners that place it at the crossroads of chromatin and DNA checkpoint pathways.

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Acknowledgments

We thank Jean-Michel Neumann for valuable comments on the manuscript. We thank Geneviève Almouzni for her enthusiasm and encouragement. This work was supported by a PIC CEA/Institut Curie on Epigenetic parameters in DNA damage response and the cell cycle, an ARC grant (4470) awarded to C.M. and an ARC grant (3828) awarded to F.O.

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  1. Florence Mousson

    Present address: Department of Physiological Chemistry, Division of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584CG, Utrecht, The Netherlands

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  1. Département de Biologie Joliot-Curie, Service de Biophysique des Fonctions Membranaires, CEA/Saclay, 91191, Gif-sur-Yvette, France

    Florence Mousson & Françoise Ochsenbein

  2. Département de Biologie Joliot-Curie, Service de Biochimie et de génétique moléculaire, CEA/Saclay, 91191, Gif-sur-Yvette, France

    Carl Mann

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Correspondence to Françoise Ochsenbein or Carl Mann.

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Communicated by G. Almouzni

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Mousson, F., Ochsenbein, F. & Mann, C. The histone chaperone Asf1 at the crossroads of chromatin and DNA checkpoint pathways. Chromosoma 116, 79–93 (2007). https://doi.org/10.1007/s00412-006-0087-z

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