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Science 21 December 2007:
Vol. 318. no. 5858, pp. 1928 - 1931
DOI: 10.1126/science.1148992
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Reports

Regulation of Replication Fork Progression Through Histone Supply and Demand

Anja Groth,1 Armelle Corpet,1 Adam J. L. Cook,1 Daniele Roche,1 Jiri Bartek,2 Jiri Lukas,2 Geneviève Almouzni1*

DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone chaperone Asf1 and MCM2–7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1–(H3-H4)–MCM2–7 intermediate and thus provides a means to fine-tune replication fork progression and histone supply and demand.

1 Laboratory of Nuclear Dynamics and Genome Plasticity, UMR218 CNRS/Institut Curie, 26 rue d'Ulm, 75248 Paris cedex 05, France.
2 Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, Copenhagen DK-2100, Denmark.

* To whom correspondence should be addressed. E-mail: Genevieve.Almouzni{at}curie.fr

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mcm Subunits Can Assemble into Two Different Active Unwinding Complexes.
D. M. Kanter, I. Bruck, and D. L. Kaplan (2008)
J. Biol. Chem. 283, 31172-31182
   Abstract »    Full Text »    PDF »
{gamma}-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin.
A. Kinner, W. Wu, C. Staudt, and G. Iliakis (2008)
Nucleic Acids Res. 36, 5678-5694
   Abstract »    Full Text »    PDF »
In Vivo Study of the Nucleosome Assembly Functions of ASF1 Histone Chaperones in Human Cells.
A. Galvani, R. Courbeyrette, M. Agez, F. Ochsenbein, C. Mann, and J.-Y. Thuret (2008)
Mol. Cell. Biol. 28, 3672-3685
   Abstract »    Full Text »    PDF »
Histone chaperone regulates replication.
R. Robinson (2008)
J. Cell Biol. 180, 250
   Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)