Title:
Connecting chromosomes and microtubules: structure and function of vertebrate kinetochore complex

Tatsuya Nishino
Department of Molecular Genetics
National Institute of Genetics

Abstract:
During mitosis, replicated sister chromatids are faithfully segregated into two daughter cells. Failure in this process causes aneuploidy and leads to cell death, developmental abnormalities or even cancer. To prevent such catastrophes, cells harbor mechanisms to ensure precise segregation. Microtubule mediated chromosome attachment is one of the mechanism. Kinetochore is a proteinacious structure built at the centromeric region of chromosomes and mediates chromosome-microtubule attachment. It is composed of more than 100 components whose function varies from DNA binding, protein-protein interaction, and microtubule binding. We recently found new chromatin binding kinetochore component CENP-T-W-S-X complex (ref. 1 and 2). We also identified mitotic phospho-regulation of CENP-T and the attachment to microtubule (ref. 3). From these results we propose a model of vertebrate kinetochore structure and regulation.

References:
1. Nishino T, Takeuchi K, Gascoigne K, Suzuki A, Hori T, Oyama T, Morikawa K, Cheeseman I, Fukagawa T (2012) CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold. Cell, 148:487-501

2 Takeuchi K, Nishino T, Mayanagi K, Horikoshi N, Osakabe A, Tachiwana H, Hori T, Kurumizaka H, Fukagawa T (2013) The centromeric nucleosome-like CENP-T-W-S-X complex forms an octamer on DNA and induces positive supercoils. Nucleic Acid Research, doi:10.1093 | nar | gkt1124

3. Nishino T, Rago F, Hori T, Tomii K, Cheeseman IM, Fukagawa T (2013) CENP-T provides a structural platform for outer kinetochore assembly. EMBO J . 32:424-36