Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway.
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.
Mello
Jill A
JA
Institut Curie, Research Section, UMR 218 du Centre National de la Recherche Scientifique (CNRS), 26 rue d'Ulm, 75248 Paris cedex 05, France.
Silljé
Herman H W
HH
Roche
Daniele M J
DM
Kirschner
Doris B
DB
Nigg
Erich A
EA
Almouzni
Geneviève
G
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
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