The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells.
The heterochromatin protein 1 (HP1)-rich heterochromatin domains next to centromeres are crucial for chromosome segregation during mitosis. This mitotic function requires their faithful reproduction during the preceding S phase, a process whose mechanism and regulation are current puzzles. Here we show that p150, a subunit of chromatin assembly factor 1, has a key role in the replication of pericentric heterochromatin and S-phase progression in mouse cells, independently of its known function in histone deposition. By a combination of depletion and complementation assays in vivo, we link this unique function of p150 to its ability to interact with HP1. Absence of this functional interaction triggers S-phase arrest at the time of replication of pericentromeric heterochromatin, without eliciting known DNA-based checkpoint pathways. Notably, in cells lacking the histone methylases Suv39h, in which pericentric domains do not show HP1 accumulation, p150 is dispensable for S-phase progression.
Quivy
Jean-Pierre
JP
lnstitut Curie, Centre de Recherche, UMR218 du CNRS, 26, rue d'Ulm, 75248 Paris cedex 05, France.
Gérard
Annabelle
A
Cook
Adam J L
AJ
Roche
Danièle
D
Almouzni
Geneviève
G
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D056504:Chromatin Assembly Factor-1; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics; D016196:S Phase / Q000502:physiology*
C533592:Chaf1a protein, mouse; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D034741:RNA, Small Interfering; D000090266:Chromobox Protein Homolog 5