一个保守的Mis12着丝粒复合体与异染色质HP1和外着丝粒蛋白Zwint-1相关联。

A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1.

作者信息

Obuse Chikashi, Iwasaki Osamu, Kiyomitsu Tomomi, Goshima Gohta, Toyoda Yusuke, Yanagida Mitsuhiro

机构信息

Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan.

出版信息

Nat Cell Biol. 2004 Nov;6(11):1135-41. doi: 10.1038/ncb1187. Epub 2004 Oct 24.

DOI:10.1038/ncb1187

PMID:15502821

Abstract

Defects in kinetochore proteins often lead to aneuploidy and cancer. Mis12-Mtw1 is a conserved, essential kinetochore protein family. Here, we show that a Mis12 core complex exists in Schizosaccharomyces pombe and human cells. Nine polypeptides bind to human hMis12; two of these, HEC1 and Zwint-1, are authentic kinetochore proteins. Four other human proteins of unknown function (c20orf172, DC8, PMF1 and KIAA1570) correspond to yeast Mis12-Mtw1 complex components and are shown to be required for chromosome segregation in HeLa cells using RNA interference (RNAi). Surprisingly, hMis12 also forms a stable complex with the centromeric heterochromatin components HP1alpha and HP1gamma. Double HP1 RNAi abolishes kinetochore localization of hMis12 and DC8. Therefore, centromeric HP1 may be the base to anchor the hMis12 core complex that is enriched with coiled coils and extends to outer Zwint-1 during mitosis.

摘要

动粒蛋白缺陷常导致非整倍体和癌症。Mis12-Mtw1是一个保守的、必不可少的动粒蛋白家族。在此，我们表明在粟酒裂殖酵母和人类细胞中存在一种Mis12核心复合体。九种多肽与人类hMis12结合；其中两种，HEC1和Zwint-1，是真正的动粒蛋白。其他四种功能未知的人类蛋白（c20orf172、DC8、PMF1和KIAA1570）对应于酵母Mis12-Mtw1复合体组分，并且使用RNA干扰（RNAi）表明它们是HeLa细胞中染色体分离所必需的。令人惊讶的是，hMis12还与着丝粒异染色质组分HP1α和HP1γ形成稳定复合体。双重HP1 RNAi消除了hMis12和DC8的动粒定位。因此，着丝粒HP1可能是锚定hMis12核心复合体的基础，该复合体富含卷曲螺旋，在有丝分裂期间延伸至外部的Zwint-1。