Regulation of replication fork progression through histone supply and demand.

Research output: Contribution to journalJournal articleResearchpeer-review

  • Groth, Anja
  • Armelle Corpet
  • Adam J L Cook
  • Daniele Roche
  • Jiri Bartek
  • Jiri Lukas
  • Geneviève Almouzni
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.
Original languageEnglish
Issue number5858
Pages (from-to)1928-31
Number of pages3
Publication statusPublished - 2007

Bibliographical note

Keywords: Cell Cycle Proteins; Chromatin; DNA; DNA Replication; DNA, Single-Stranded; Hela Cells; Histones; Humans; Models, Biological; Molecular Chaperones; Nuclear Proteins; Nucleosomes; RNA Interference; S Phase

ID: 5013946