Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 15, Issue 9, Pages 972-979Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1470
Keywords
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Funding
- Delegation Generale pour l'Armement [DGA/DSP/STTC/DT/SH]
- Association pour la Recherche sur la Cancer
- Ligue Nationale Contre le Cancer
- 'Retinoblastome' and 'Replication, Instabilite chromosomique et cancer'
- European Commission Network of Excellence Epigenome [LSHG-CT-2004-503433]
- ANR [NT05-4_42267, PCV06_142302]
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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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