A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1
A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1
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DOI：
10.1038/ncb1187
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发表时间：
2004-11-01
影响因子：
21.3
通讯作者：
Yanagida, M
中科院分区：
文献类型：
--
作者：
Obuse, C;Iwasaki, O;Yanagida, M
动粒蛋白的缺陷往往会导致非整倍体和癌症。MIS12-MTW1是一个保守的、必需的动粒蛋白家族。在这里，我们发现在裂殖酵母和人类细胞中存在Mis12核心复合体。9个多肽与人hMis12结合；其中两个，HEC1和Zwint-1，是真正的动粒蛋白。另外四种未知功能的人类蛋白质(c20orf172、dc8、PMF1和KIAA1570)对应于酵母Mis12-MTW1复杂成分，并通过RNA干扰(RNAi)被证明是HeLa细胞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成分HP1pha和HP1Gamma形成稳定的复合体。双重HP1 RNAi取消了hMis12和DC8的动粒定位。因此，着丝粒HP1可能是锚定hMis12核心复合体的碱基，该复合体在有丝分裂过程中富含卷曲并延伸到外部Zwint-1。
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.