HJURP Is a Cell-Cycle-Dependent Maintenance and Deposition Factor of CENP-A at Centromeres

被引:505
作者
Dunleavy, Elaine M. [1 ]
Roche, Daniele [1 ]
Tagami, Hideaki [2 ]
Lacoste, Nicolas [1 ]
Ray-Gallet, Dominique [1 ]
Nakamura, Yusuke [3 ]
Daigo, Yataro [3 ]
Nakatani, Yoshihiro [2 ]
Almouzni-Pettinotti, Genevieve [1 ]
机构
[1] Inst Curie, CNRS, Lab Nucl Dynam & Genome Plast, UMR218, F-75248 Paris 05, France
[2] Nagoya City Univ, Grad Sch Nat Sci, Mizuho Ku, Aichi 4678501, Japan
[3] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo 1130033, Japan
关键词
HISTONE H3 VARIANT; FISSION YEAST SCM3; BUDDING YEAST; CHROMATIN; PROTEIN; KINETOCHORE; COMPLEX; NUCLEOSOME; CHAPERONE; DNA;
D O I
10.1016/j.cell.2009.02.040
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The histone H3 variant CenH3, called CENP-A in humans, is central in centromeric chromatin to ensure proper chromosome segregation. In the absence of an underlying DNA sequence, it is still unclear how CENP-A deposition at centromeres is determined. Here, we purified non-nucleosomal CENP-A complexes to identify direct CENP-A partners involved in such a mechanism and identified HJURP. HJURP was not detected in H3.1- or H3.3-containing complexes, indicating its specificity for CENP- A. HJURP centromeric localization is cell cycle regulated, and its transient appearance at the centromere coincides precisely with the proposed time window for new CENP- A deposition. Furthermore, HJURP downregulation leads to a major reduction in CENP-A at centromeres and impairs deposition of newly synthesized CENP-A, causing mitotic defects. We conclude that HJURP is a key factor for CENP-A deposition and maintenance at centromeres.
引用
收藏
页码:485 / 497
页数:13
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