CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression
- Title
- CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression
- Author
- 채영규
- Keywords
- CHROMATIN-REMODELING COMPLEX; HISTONE H3 METHYLATION; PERICENTRIC HETEROCHROMATIN; DNA-REPLICATION; DEPENDENT KINASES; FISSION YEAST; CANCER-CELLS; SET DOMAIN; HP1; MAINTENANCE
- Issue Date
- 2014-04
- Publisher
- Oxford University Press
- Citation
- Nucleic acids research , Vol.42 No.10 [2014] , 6196-6207
- Abstract
- Although several studies have suggested that the functions of heterochromatin regulators may be regulated by post-translational modifications during cell cycle progression, regulation of the histone methyltransferase Suv39H1 is not fully understood. Here, we demonstrate a direct link between Suv39H1 phosphorylation and cell cycle progression. We show that CDK2 phosphorylates Suv39H1 at Ser391 and these phosphorylation levels oscillate during the cell cycle, peaking at S phase and maintained during S-G2-M phase. The CDK2-mediated phosphorylation of Suv39H1 at Ser391 results in preferential dissociation from chromatin. Furthermore, phosphorylation-mediated dissociation of Suv39H1 from chromatin causes an enhanced occupancy of JMJD2A histone demethylase on heterochromatin and alterations in inactive histone marks. Overexpression of phospho-mimic Suv39H1 induces early replication of heterochromatin, suggesting the importance of Suv39H1 phosphorylation in the replication of heterochromatin. Moreover, overexpression of phospho-defective Suv39H1 caused altered replication timing of heterochromatin and increases sensitivity to replication stress. Collectively, our data suggest that phosphorylation-mediated modulation of Suv39H1-chromatin association may be an initial step in heterochromatin replication.
- URI
- https://academic.oup.com/nar/article/42/10/6196/2435207http://hdl.handle.net/20.500.11754/51641
- ISSN
- 0305-1048; 1362-4962
- DOI
- 10.1093/nar/gku263
- Appears in Collections:
- GRADUATE SCHOOL[S](대학원) > ETC
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