期刊
CELL CYCLE
卷 9, 期 21, 页码 4351-4363出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.21.13596
关键词
Cdt1; HBO1; HDAC11; chromatin; DNA replication
类别
资金
- American Heart Association
- National Functional Genomics Center at the Moffitt Cancer Center
- Florida Department of Health
- James and Esther King Foundation [06-NIR-01]
- NCI [P50-CA119997, CA130865]
The efficiency of metazoan origins of DNA replication is known to be enhanced by histone acetylation near origins. Although this correlates with increased MCM recruitment, the mechanism by which such acetylation regulates MCM loading is unknown. We show here that Cdt1 induces large-scale chromatin decondensation that is required for MCM recruitment. This process occurs in G(1), is suppressed by Geminin, and requires HBO1 HAT activity and histone H4 modifications. HDAC11, which binds Cdt1 and replication origins during S-phase, potently inhibits Cdt1-induced chromatin unfolding and re-replication, suppresses MCM loading and binds Cdt1 more efficiently in the presence of Geminin. We also demonstrate that chromatin at endogenous origins is more accessible in G(1) relative to S-phase. These results provide evidence that histone acetylation promotes MCM loading via enhanced chromatin accessibility. This process is regulated positively by Cdt1 and HBO1 in G(1) and repressed by Geminin-HDAC11 association with Cdt1 in S-phase, and represents a novel form of replication licensing control.
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