The kinetochore proteins Pcs1 and Mde4 and heterochromatin are required to prevent merotelic orientation

被引:73
作者
Gregan, Juraj
Riedel, Christian G.
Pidoux, Alison L.
Katou, Yuki
Rumpf, Cornelia
Schleiffer, Alexander
Kearsey, Stephen E.
Shirahige, Katsuhiko
Allshire, Robin C.
Nasmyth, Kim
机构
[1] Univ Vienna, Dept Chromosome Biol, Max F Perutz Labs, A-1030 Vienna, Austria
[2] Res Inst Mol Pathol, A-1030 Vienna, Austria
[3] Univ Edinburgh, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland
[4] Univ Oxford, Dept Zool, Oxford OX1 3PS, England
[5] Tokyo Inst Technol, Ctr Biol Resources & Informat, Div Gen Res, Lab Genome Struct & Funct, Yokohama, Kanagawa 2268501, Japan
基金
英国惠康基金;
关键词
D O I
10.1016/j.cub.2007.06.044
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Accurate chromosome segregation depends on the establishment of correct-amphitelickinetochore orientation. Merotelic kinetochore orientation is an error that occurs when a single kinetochore attaches to microtubules emanating from opposite spindle poles, a condition that hinders segregation of the kinetochore to a spindle pole in anaphase. To avoid chromosome missegregation resulting from merotelic kinetochore orientation, cells have developed mechanisms to prevent or correct merotelic attachment. A protein called Pcs1 has been implicated in preventing merotelic attachment in mitosis and meiosis II in the fission yeast S. pombe. Results: We report that Pcs1 forms a complex with a protein called Mde4. Both Pcs1 and Mde4 localize to the central core of centromeres. Deletion of mde4(+), like that of pcs1(+), causes the appearance of lagging chromosomes during the anaphases of mitotic and meiosis II cells. We provide evidence that the kinetochores of lagging chromosomes in both pcs1 and mde4 mutant cells are merotelically attached. In addition, we find that lagging chromosomes in cells with defective centromeric heterochromatin also display features consistent with merotelic attachment. Conclusions: We suggest that the Pcs1/Mde4 complex is the fission yeast counterpart of the budding yeast monopolin subcomplex Csm1/Lrs4, which promotes the segregation of sister kinetochores to the same pole during meiosis I. We propose that the Pcs1/Mde4 complex acts in the central kinetochore domain to clamp microtubule binding sites together, the centromeric heterochromatin coating the flanking domains provides rigidity, and both systems contribute to the prevention of merotelic attachment.
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页码:1190 / 1200
页数:11
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