Genome-wide analysis reveals a cell cycle-dependent mechanism controlling centromere propagation

被引：143

作者：

Erhardt, Sylvia ^{[2
,3
,4
]}

Mellone, Barbara G. ^{[2
,3
]}

Betts, Craig M. ^{[1
]}

Zhang, Weiguo ^{[2
,3
]}

Karpen, Gary H. ^{[2
,3
]}

Straight, Aaron F. ^{[1
]}

机构：

[1] Stanford Med Sch, Dept Biochem, Stanford, CA 94305 USA

[2] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Genome Dynam, Berkeley, CA 94720 USA

[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[4] Heidelberg Univ, Zentrum Mol Biol, D-69120 Heidelberg, Germany

来源：

JOURNAL OF CELL BIOLOGY | 2008年 / 183卷 / 05期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

D O I：

10.1083/jcb.200806038

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Centromeres are the structural and functional foundation for kinetochore formation, spindle attachment, and chromosome segregation. In this study, we isolated factors required for centromere propagation using genome-wide RNA interference screening for defects in centromere protein A (CENP-A; centromere identifier [CID]) localization in Drosophila melanogaster. We identified the proteins CAL1 and CENP-C as essential factors for CID assembly at the centromere. CID, CAL1, and CENP-C coimmunoprecipitate and are mutually dependent for centromere localization and function. We also identified the mitotic cyclin A (CYCA) and the anaphase-promoting complex (APC) inhibitor RCA1/Emil as regulators of centromere propagation. We show that CYCA is centromere localized and that CYCA and RCA1/Emil couple centromere assembly to the cell cycle through regulation of the fizzy-related/CDH1 subunit of the APC. Our findings identify essential components of the epigenetic machinery that ensures proper specification and propagation of the centromere and suggest a mechanism for coordinating centromere inheritance with cell division.

引用

页码：805 / 818

页数：14

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