Human Zwint-1 Specifies Localization of Zeste White 10 to Kinetochores and Is Essential for Mitotic Checkpoint Signaling  

作　　者：HongmeiWang XiaoyuHu XiaDing ZhenDou ZhihongYank AndrewW.Shaw MaikunTcng DonW.Cleveland MichaelL.Goldberg LiwenNiu XucbiaoYao 

机构地区：[1]FromtheCASKeyLaboratoryforStructureBiologyandHefeiNationalLaboratoryforPhysisicalSciencesatMicroscale,Hefei230027,China,theDepartmentofPhysiology,MorehouseSchoolofMedicine,Atlanta,Georgia30310,Proteomics

出　　处：《中国生物学文摘》2005年第4期67-75,共9页Chinese Biological Abstracts

摘　　要：Chromosome segregation in mitosis is orchestrated by dynamic interaction between spindle microtubules and the kinetochore, a multiprotein complex assembled onto centromeric DNA of the chromosome. Here we show that Zwint-1 is required and is sufficient for kinetochore localization of Zestc White 10 (ZW10) in HeLa cells. Zwint-1 specifies the kinetochore association of ZW10 by interacting with its N-terminal domain. Suppression of synthesis of Zwint-1 by small interfering RNA abolishes the localization of ZW10 to the kinetochore, demonstrating the requirement of Zwint-1 for ZWl0 kinetochore localization. In addition, dcplction of Zwint-1 affects no mitotic arrest but causes aberrant premature chromo. some segregation. These Zwint-l-suppressed cells dis. play chromosome bridge phenotype with sister chromatids inter-connected. Moreover, Zwint-1 is required for stable association of CENP.F and dynamitin but not BUB1 with the kinetochore. Finally, our studies showthat Zwint-1 is a new component of the mitotic check. point, as cells lacking Zwint-1 fail to arrest in mitosis when exposed to microtubule inhibitors, yielding inter. phase cells with multinuclei. As ZWl0 and Zwint.1 are absent from yeast, we reasoned that metazoans evolved an elaborate spindle checkpoint machinery to ensure faithful chromosome segregation in mitosis.

关 键 词：染色体 有丝分裂 着丝点 Zwint-1定位 

分 类 号：Q343.2[生物学—遗传学]