Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint

Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint
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DOI:
10.1128/mcb.18.5.2738
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发表时间:
1998-05-01
影响因子:
5.3
通讯作者:
Hoyt, MA
Hoyt, MA
中科院分区:
生物学2区
文献类型:
--
作者:
Farr, KA;Hoyt, MA

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酿酒酵母BUB 1编码纺锤体组装检查点功能所需的蛋白激酶,在纺锤体损伤的情况下,需要BUB 1来阻止细胞周期进展到后期,我们已经鉴定出一个占主导地位的作用BUB 1等位基因,它似乎激活纺锤体组装检查点途径在纺锤体未受损的细胞中。BUB 1 -5的高水平表达并没有引起可检测的纺锤体损伤,但它延迟了酵母细胞在有丝分裂中的一个阶段,双极纺锤体组装后,但在后期纺锤体伸长。延迟的细胞具有G(2)DNA含量和升高的Clb 2 p有丝分裂细胞周期蛋白水平。与纺锤体损伤或MPS 1激酶过表达导致有丝分裂延迟的细胞不同,Mad 1 p检查点蛋白的过度磷酸化形式没有积累。与过表达MPS 1的细胞类似,BUB 1 -5延迟依赖于其他检查点基因的功能,包括BUB 2和BUB 3以及MAD 1,MAD 2和MAD 3。我们发现BUB 1 -5或MPS 1过表达所引起的有丝分裂延迟是相互依赖的。这表明Bub 1 p和Mps 1 p激酶在产生纺锤体损伤信号的早期步骤中一起起作用。
Saccharomyces cerevisiae BUB1 encodes a protein kinase required for spindle assembly checkpoint function, In the presence of spindle damage, BUB1 is required to prevent cell cycle progression into anaphase, We have identified a dominantly acting BUB1 allele that appears to activate the spindle assembly checkpoint pathway in cells with undamaged spindles. High-level expression of BUB1-5 did not cause detectable spindle damage, yet it delayed yeast cells in mitosis at a stage following bipolar spindle assembly but prior to anaphase spindle elongation. Delayed cells possessed a G(2) DNA content and elevated Clb2p mitotic cyclin levels. Unlike cells delayed in mitosis by spindle damage or MPS1 kinase overexpression, hyperphosphorylated forms of the Mad1p checkpoint protein did not accumulate. Similar to cells overexpressing MPS1, the BUB1-5 delay was dependent upon the functions of the other checkpoint genes, including BUB2 and BUB3 and MAD1, MAD2, and MAD3. We found that the mitotic delay caused by BUB1-5 or MPS1 overexpression was interdependent upon the function of the other. This suggests that the Bub1p and Mps1p kinases act together at an early step in generating the spindle damage signal.