title: Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway.
abstract: The efficient assembly of newly replicated and repaired DNA into chromatin is essential for proper genome function. Based on genetic studies in Saccharomyces cerevisiae, the histone chaperone anti-silencing function 1 (Asf1) has been implicated in the DNA repair response. Here, the human homologs are shown to function synergistically with human CAF-1 to assemble nucleosomes during nucleotide excision repair in vitro. Furthermore, we demonstrate that hAsf1 proteins can interact directly with the p60 subunit of hCAF-1. In contrast to hCAF-1 p60, the nuclear hAsf1 proteins are not significantly associated with chromatin in cells before or after the induction of DNA damage, nor specifically recruited to damaged DNA during repair in a bead-linked DNA assay. A model is proposed in which the synergism between hAsf1 and CAF-1 for nucleosome formation during DNA repair is achieved through a transient physical interaction allowing histone delivery from Asf1 to CAF-1.
authors.affiliation: Institut Curie, Research Section, UMR 218 du Centre National de la Recherche Scientifique (CNRS), 26 rue d'Ulm, 75248 Paris cedex 05, France.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Mello
authors.forename: Herman H W
authors.initials: HH
authors.lastname: Silljé
authors.forename: Daniele M J
authors.initials: DM
authors.lastname: Roche
authors.forename: Doris B
authors.initials: DB
authors.lastname: Kirschner
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.forename: Geneviève
authors.initials: G
authors.lastname: Almouzni
mesh_terms: D018797:Cell Cycle Proteins / Q000502:physiology*; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism; D056489:Nucleoplasmins; D009707:Nucleosomes / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C491641:ASF1A protein, human; C491640:ASF1B protein, human; C533593:CHAF1B protein, human; D018797:Cell Cycle Proteins; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D056489:Nucleoplasmins; D009707:Nucleosomes; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; C425323:TLK1 protein, human