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Nat Struct Mol Biol. 2008 Sep;15(9):972-9.

The HP1-p150/CAF-1 interaction is required for pericentric heterochromatin replication and S-phase progression in mouse cells.

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lnstitut Curie, Centre de Recherche, UMR218 du CNRS, 26, rue d'Ulm, 75248 Paris cedex 05, France.


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.

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