Regulation of Replication Fork Progression Through Histone Supply and Demand
Date
2007
Authors
Groth, Anja
Corpet, Armelle
Cook, Adam
Roche, Daniele
Bartek, Jiri
Lukas, Jiri
Almouzni, Genevieve
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American Association for the Advancement of Science
Abstract
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.
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Keywords: chaperone; forkhead transcription factor; helicase; histone; histone H3; histone H4; minichromosome maintenance protein 7; protein asf1; unclassified drug; DNA; enzyme activity; eukaryote; genetics; protein; RNA; animal cell; article; chromatin; chromosom
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Journal article
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2037-12-31
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