2. Academic Validation
  3. CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore

CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore

  • Cell. 2008 Dec 12;135(6):1039-52. doi: 10.1016/j.cell.2008.10.019.
Tetsuya Hori 1,  Miho Amano,  Aussie Suzuki,  Chelsea B Backer,  Julie P Welburn,  Yimin Dong,  Bruce F McEwen,  Wei-Hao Shang,  Emiko Suzuki,  Katsuya Okawa,  Iain M Cheeseman,  Tatsuo Fukagawa
Affiliations

Affiliation

  • 1 Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan.
PMID: 19070575 DOI: 10.1016/j.cell.2008.10.019
Abstract

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.

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