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

被引:219
作者
Obuse, C [1 ]
Iwasaki, O [1 ]
Kiyomitsu, T [1 ]
Goshima, G [1 ]
Toyoda, Y [1 ]
Yanagida, M [1 ]
机构
[1] Kyoto Univ, Grad Sch Biostudies, Dept Gene Mech, Sakyo Ku, Kyoto 6068501, Japan
关键词
D O I
10.1038/ncb1187
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1135 / U37
页数:12
相关论文
共 35 条
[1]   INCENP centromere and spindle targeting: Identification of essential conserved motifs and involvement of heterochromatin protein HP1 [J].
Ainsztein, AM ;
Kandels-Lewis, SE ;
Mackay, AM ;
Earnshaw, WC .
JOURNAL OF CELL BIOLOGY, 1998, 143 (07) :1763-1774
[2]   Building the centromere: from foundation proteins to 3D organization [J].
Amor, DJ ;
Kalitsis, P ;
Sumer, H ;
Choo, KHA .
TRENDS IN CELL BIOLOGY, 2004, 14 (07) :359-368
[3]   The role of Drosophila CID in kinetochore formation, cell-cycle progression and heterochromatin interactions [J].
Blower, MD ;
Karpen, GH .
NATURE CELL BIOLOGY, 2001, 3 (08) :730-739
[4]   Hierarchical assembly of the budding yeast kinetochore from multiple subcomplexes [J].
De Wulf, P ;
McAinsh, AD ;
Sorger, PK .
GENES & DEVELOPMENT, 2003, 17 (23) :2902-2921
[5]   Nuf2 and Hec1 are required for retention of the checkpoint proteins Mad1 and Mad2 to kinetochores [J].
DeLuca, JG ;
Howell, BJ ;
Canman, JC ;
Hickey, JM ;
Fang, GW ;
Salmon, ED .
CURRENT BIOLOGY, 2003, 13 (23) :2103-2109
[6]   Nnf1p, Dsn1p, Mtw1p, and Nsl1p:: a new group of proteins important for chromosome segregation in Saccharomyces cerevisiae [J].
Euskirchen, GM .
EUKARYOTIC CELL, 2002, 1 (02) :229-240
[7]   The role of Ppe1/PP6 phosphatase for equal chromosome segregation in fission yeast kinetochore [J].
Goshima, G ;
Iwasaki, O ;
Obuse, C ;
Yanagida, M .
EMBO JOURNAL, 2003, 22 (11) :2752-2763
[8]   Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation [J].
Goshima, G ;
Saitoh, S ;
Yanagida, M .
GENES & DEVELOPMENT, 1999, 13 (13) :1664-1677
[9]   Human centromere chromatin protein hMis12, essential for equal segregation, is independent of CENP-A loading pathway [J].
Goshima, G ;
Kiyomitsu, T ;
Yoda, K ;
Yanagida, M .
JOURNAL OF CELL BIOLOGY, 2003, 160 (01) :25-39
[10]   Cell cycle behavior of human HP1 subtypes: distinct molecular domains of HP1 are required for their centromeric localization during interphase and metaphase [J].
Hayakawa, T ;
Haraguchi, T ;
Masumoto, H ;
Hiraoka, Y .
JOURNAL OF CELL SCIENCE, 2003, 116 (16) :3327-3338