期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 12, 页码 8326-8336出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.529958
关键词
Cell Division; Centromeres; Chromatin Structure; Histone Chaperone; Phosphorylation
资金
- National Institutes of Health [DK56292, CA164133, 8G12MD007602, G12RR03034]
- Chinese 973 Projects [2010CB912103, 2012CB917204, 2013CB911203]
- Chinese Academy of Science [KSCX1-YW-R-65, KSCX2-YW-R-195]
- MOST [2009DFA31010]
- MOE [20113402130010, IRT13038]
- Chinese Natural Science Foundation [91313303, 31320103904, 90508002, 91129714, 81270466, 31271518, 31371363, 90913016]
- China Fellowship [2012M510210]
- Fundamental Research Funds for Central Universities [WK2340000032, WK2060190018]
Background: HJURP is a molecular chaperone essential for the deposition of the centromere marker CENP-A. Results: Mis18 binds with and specifies the centromere localization of HJURP. Conclusion: Mis18 governs centromere assembly via the Mis18-HJURP-CENP-A axis. Significance: Our finding reveals a novel mechanism underlying CENP-A incorporation into the centromere. The centromere is essential for precise and equal segregation of the parental genome into two daughter cells during mitosis. CENP-A is a unique histone H3 variant conserved in eukaryotic centromeres. The assembly of CENP-A to the centromere is mediated by Holliday junction recognition protein (HJURP) in early G(1) phase. However, it remains elusive how HJURP governs CENP-A incorporation into the centromere. Here we show that human HJURP directly binds to Mis18, a component of the Mis18 complex conserved in the eukaryotic kingdom. A minimal region of HJURP for Mis18 binding was mapped to residues 437-460. Depletion of Mis18 by RNA interference dramatically impaired HJURP recruitment to the centromere, indicating the importance of Mis18 in HJURP loading. Interestingly, phosphorylation of HJURP by CDK1 weakens its interaction with Mis18, consistent with the notion that assembly of CENP-A to the centromere is achieved after mitosis. Taken together, these data define a novel molecular mechanism underlying the temporal regulation of CENP-A incorporation into the centromere by accurate Mis18-HJURP interaction.
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