CCAN Makes Multiple Contacts with Centromeric DNA to Provide Distinct Pathways to the Outer Kinetochore

被引：327

作者：

Hori, Tetsuya ^{[1
]}

Amano, Miho ^{[1
]}

Suzuki, Aussie ^{[1
]}

Backer, Chelsea B. ^{[3
,4
]}

Welburn, Julie P. ^{[3
,4
]}

Dong, Yimin ^{[5
]}

McEwen, Bruce F. ^{[5
]}

Shang, Wei-Hao ^{[1
]}

Suzuki, Emiko ^{[2
]}

Okawa, Katsuya ^{[6
]}

Cheeseman, Iain M. ^{[3
,4
]}

Fukagawa, Tatsuo ^{[1
]}

机构：

[1] Natl Inst Genet, Dept Mol Genet, Mishima, Shizuoka 4118540, Japan

[2] Natl Inst Genet, Struct Biol Ctr, Mishima, Shizuoka 4118540, Japan

[3] MIT, Cambridge Ctr 9, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[4] MIT, Cambridge Ctr 9, Dept Biol, Cambridge, MA 02142 USA

[5] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA

[6] Kyoto Univ, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan

来源：

CELL | 2008年 / 135卷 / 06期

关键词：

D O I：

10.1016/j.cell.2008.10.019

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：

Kinetochore specification and assembly requires the targeted deposition of specialized nucleosomes containing the histone H3 variant CENP-A at centromeres. However, CENP-A is not sufficient to drive full-kinetochore assembly, and it is not clear how centromeric chromatin is established. Here, we identify CENP-W as a component of the DNA-proximal constitutive centromere-associated network (CCAN) of proteins. We demonstrate that CENP-W forms a DNA-binding complex together with the CCAN component CENP-T. This complex directly associates with nucleosomal DNA and with canonical histone H3, but not with CENP-A, in centromeric regions. CENP-T/CENP-W functions upstream of other CCAN components with the exception of CENP-C, an additional putative DNA-binding protein. Our analysis indicates that CENP-T/CENP-W and CENP-C provide distinct pathways to connect the centromere with outer kinetochore assembly. In total, our results suggest that the CENP-T/CENP-W complex is directly involved in establishment of centromere chromatin structure coordinately with CENP-A.

引用

页码：1039 / 1052

页数：14

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