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演者: Arshad Desai 博士

Ludwig Institute for Cancer Research

University of California&s_comma; San Diego&s_comma; USA

演題:Kinetochore Specification and Function

日時:12月 10日 (月) 1 5:00~16:00

場所: 東京大学分子細胞生物学研究所総合研究棟2階会議室

We are investigating the molecular mechanisms of kinetochore specification and kinetochore-spindle microtubule attachment. Using in vivo assays in the C. elegans embryo and RNAi-based functional genomics&s_comma; we identified a set of 5 proteins&s_comma; including the centromeric histone CENP-A&s_comma; whose inhibition results in a “kinetochore-null” phenotype. One of these&s_comma; KNL-2&s_comma; defined a conserved subfamily of Myb/SANT DNA-binding domain-containing proteins specifically required for CENP-A loading. Two of the other KNLs&s_comma; KNL-1 and KNL-3&s_comma; are part of a group of 10 interacting kinetochore proteins&s_comma; referred to as the KMN (KNL-1/Mis12 complex/Ndc80 complex) network. In vivo analysis and in vitro reconstitutions indicates that the KMN network constitutes the core microtubule-binding site of the kinetochore. We propose that multivalent interactions comprised of intrinsically low affinity binding sites within the KMN network generate the dynamic kinetochore-microtubule interface.