Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis

被引:87
作者
Fernius, Josefin [1 ]
Hardwick, Kevin G. [1 ]
机构
[1] Univ Edinburgh, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH8 9YL, Midlothian, Scotland
来源
PLOS GENETICS | 2007年 / 3卷 / 11期
基金
英国惠康基金;
关键词
D O I
10.1371/journal.pgen.0030213
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
During cell division all chromosomes must be segregated accurately to each daughter cell. Errors in this process give rise to aneuploidy, which leads to birth defects and is implicated in cancer progression. The spindle checkpoint is a surveillance mechanism that ensures high fidelity of chromosome segregation by inhibiting anaphase until all kinetochores have established bipolar attachments to spindle microtubules. Bub1 kinase is a core component of the spindle checkpoint, and cells lacking Bub1 fail to arrest in response to microtubule drugs and precociously segregate their DNA. The mitotic role( s) of Bub1 kinase activity remain elusive, and it is controversial whether this C-terminal domain of Bub1p is required for spindle checkpoint arrest. Here we make a detailed analysis of budding yeast cells lacking the kinase domain (bub1 Delta K). We show that despite being able to arrest in response to microtubule depolymerisation and kinetochore-microtubule attachment defects, bub1DK cells are sensitive to microtubule drugs. This is because bub1DK cells display significant chromosome mis-segregation upon release from nocodazole arrest. bub1DK cells mislocalise Sgo1p, and we demonstrate that both the Bub1 kinase domain and Sgo1p are required for accurate chromosome biorientation after nocodazole treatment. We propose that Bub1 kinase and Sgo1p act together to ensure efficient biorientation of sister chromatids during mitosis.
引用
收藏
页码:2312 / 2325
页数:14
相关论文
共 74 条
  • [1] Aurora B regulates MCAK at the mitotic centromere
    Andrews, PD
    Ovechkina, Y
    Morrice, N
    Wagenbach, M
    Duncan, K
    Wordeman, L
    Swedlow, JR
    [J]. DEVELOPMENTAL CELL, 2004, 6 (02) : 253 - 268
  • [2] Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis
    Bernard, P
    Hardwick, K
    Javerzat, JP
    [J]. JOURNAL OF CELL BIOLOGY, 1998, 143 (07) : 1775 - 1787
  • [3] The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the, spindle checkpoint
    Biggins, S
    Murray, AW
    [J]. GENES & DEVELOPMENT, 2001, 15 (23) : 3118 - 3129
  • [4] Complex formation between Mad1p, Bub1p and Bub3p is crucial for spindle checkpoint function
    Brady, DM
    Hardwick, KG
    [J]. CURRENT BIOLOGY, 2000, 10 (11) : 675 - 678
  • [5] CHAN CSM, 1993, GENETICS, V135, P677
  • [6] Spindle checkpoint protein Xmad1 recruits Xmad2 to unattached kinetochores
    Chen, RH
    Shevchenko, A
    Mann, M
    Murray, AW
    [J]. JOURNAL OF CELL BIOLOGY, 1998, 143 (02) : 283 - 295
  • [7] Centromeres and kinetochores: From epigenetics to mitotic checkpoint signaling
    Cleveland, DW
    Mao, YH
    Sullivan, KF
    [J]. CELL, 2003, 112 (04) : 407 - 421
  • [8] Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p
    CohenFix, O
    Peters, JM
    Kirschner, MW
    Koshland, D
    [J]. GENES & DEVELOPMENT, 1996, 10 (24) : 3081 - 3093
  • [9] Goldstein AL, 1999, YEAST, V15, P1541, DOI 10.1002/(SICI)1097-0061(199910)15:14<1541::AID-YEA476>3.0.CO
  • [10] 2-K