Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis.

Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis.
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DOI:
10.1083/jcb.143.7.1775
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发表时间:
1998-12-28
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Javerzat JP
Javerzat JP
中科院分区:
其他
文献类型:
--
作者:
Bernard P;Hardwick K;Javerzat JP

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纺锤体检查点通过延迟后期直到所有染色体正确地附着到有丝分裂纺锤体来确保正确的染色体分离。我们研究了分裂酵母bub1基因在纺锤体检查点功能和未受干扰的有丝分裂中的作用。我们发现,bub1 +是必不可少的分裂酵母纺锤体检查点响应纺锤体损伤和缺陷的着丝粒功能。检查点的激活导致Bub1被募集到着丝粒,并延迟有丝分裂的完成。我们发现,Bub1也有一个正常的,不受干扰的有丝分裂的关键作用。bub1功能的丧失导致染色体在后期纺锤体上滞后,并增加染色体丢失的频率。这种基因组不稳定性在Δbub1二倍体中甚至更加显著,导致大量染色体错误分离事件和二倍体状态的丧失,表明bub1 +功能对于通过有丝分裂维持正确的倍性至关重要。在较大的真核生物中,Bub1在有丝分裂的早期阶段被招募到动粒中。然而,与脊椎动物不同的是,Bub1的池在中期甚至直到末期仍然与着丝粒相关。我们讨论了Bub1激酶的中期后期过渡后的作用的可能性。
The spindle checkpoint ensures proper chromosome segregation by delaying anaphase until all chromosomes are correctly attached to the mitotic spindle. We investigated the role of the fission yeast bub1 gene in spindle checkpoint function and in unperturbed mitoses. We find that bub1 + is essential for the fission yeast spindle checkpoint response to spindle damage and to defects in centromere function. Activation of the checkpoint results in the recruitment of Bub1 to centromeres and a delay in the completion of mitosis. We show that Bub1 also has a crucial role in normal, unperturbed mitoses. Loss of bub1 function causes chromosomes to lag on the anaphase spindle and an increased frequency of chromosome loss. Such genomic instability is even more dramatic in Δbub1 diploids, leading to massive chromosome missegregation events and loss of the diploid state, demonstrating that bub1 + function is essential to maintain correct ploidy through mitosis. As in larger eukaryotes, Bub1 is recruited to kinetochores during the early stages of mitosis. However, unlike its vertebrate counterpart, a pool of Bub1 remains centromere-associated at metaphase and even until telophase. We discuss the possibility of a role for the Bub1 kinase after the metaphase–anaphase transition.