Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis.
Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis.
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DOI：
10.1371/journal.pgen.0030213
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发表时间：
2007-11
期刊：
影响因子：
4.5
通讯作者：
Hardwick KG
中科院分区：
文献类型：
--
作者：
Fernius J;Hardwick KG
在细胞分裂期间，所有的染色体必须准确地分离到每个子细胞。这个过程中的错误会导致非整倍体，从而导致出生缺陷，并与癌症进展有关。纺锤体检查点是一种监视机制，通过抑制后期，直到所有着丝点都与纺锤体微管建立双极性附着，确保染色体分离的高保真度。Bub1激酶是纺锤体检查点的核心组成部分，缺乏Bub1的细胞在对微管药物的反应中不能被抑制，并且过早地分离它们的DNA。Bub1激酶活性的有丝分裂作用仍然是难以捉摸的，并且Bub1p的c端结构域是否需要纺锤体检查点阻滞是有争议的。在这里，我们对缺乏激酶结构域的出芽酵母细胞进行了详细分析（bub1ΔK）。我们表明，尽管能够对微管解聚合和着丝点-微管附着缺陷做出反应，bub1ΔK细胞对微管药物敏感。这是因为bub1ΔK细胞从诺可达唑阻滞中释放后显示出显著的染色体错误分离。bub1ΔK细胞错误定位Sgo1p，我们证明在诺可达唑处理后，Bub1激酶结构域和Sgo1p都是精确的染色体双取向所必需的。我们提出Bub1激酶和Sgo1p共同作用，以确保姐妹染色单体在有丝分裂过程中有效的双向定向。许多人类疾病，包括出生缺陷和癌症，都与非整倍体有关。这是细胞染色体数量不正确的地方，因为在细胞分裂过程中不能准确地分离它们的遗传物质。细胞采用许多控制机制来确保染色体分离的极高保真度。它们这样做的一种方式是将染色体的复制副本（称为姐妹染色单体）固定在一起，直到它们都正确地附着在有丝分裂纺锤体的微管上。所有成对的姐妹染色单体必须有一个姐妹附着在两个纺锤杆上，这个过程被称为双取向。在这里，我们证明了Bub1激酶结构域将Sgo1靶向出芽酵母着丝粒，并且这两种蛋白都是酵母有丝分裂中染色体有效的双向定向所必需的。在抗菌素小管药物治疗后的纺锤体重组过程中，Bub1激酶和Sgo1的功能变得尤为重要。我们认为这是因为突变细胞对没有张力的着丝点没有反应，并且它们不能纠正两个姐妹染色单体附着在同一纺锤极的微管上的合丝附着。
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 (bub1ΔK). We show that despite being able to arrest in response to microtubule depolymerisation and kinetochore-microtubule attachment defects, bub1ΔK cells are sensitive to microtubule drugs. This is because bub1ΔK cells display significant chromosome mis-segregation upon release from nocodazole arrest. bub1ΔK 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. Many human diseases, including birth defects and cancer, are associated with aneuploidy. This is where cells have an incorrect number of chromosomes, because of a failure to segregate their genetic material accurately during cell division. Cells employ many control mechanisms to ensure an extremely high fidelity of chromosome segregation. One way that they do this is to hold the replicated copies of their chromosomes (known as sister chromatids) together until they are all attached properly to microtubules of the mitotic spindle. All pairs of sister chromatids must have one sister attached to each of the two spindle poles, a process known as biorientation. Here we demonstrate that the Bub1 kinase domain acts to target Sgo1 to budding yeast centromeres, and that both of these proteins are required for efficient biorientation of chromosomes in yeast mitosis. Bub1 kinase and Sgo1 functions become particularly important during spindle reassembly after antimicrotubule drug treatment. We propose that this is because the mutant cells fail to respond to kinetochores that are not under tension, and that they are unable to correct syntelic attachments where both sister chromatids attach to microtubules from the same spindle pole.
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影响因子：
10.5
作者：
CohenFix, O;Peters, JM;Koshland, D
通讯作者：
Koshland, D
影响因子：
9.2
作者：
Indjeian, Vahan B.;Murray, Andrew W.
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DOI：
10.1083/jcb.143.7.1775
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
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影响因子：
9.2
作者：
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通讯作者：
Nasmyth, K
影响因子：
4
作者：
Johnson, VL;Scott, MIF;Taylor, SS
通讯作者：
Taylor, SS