Bernard P, Hardwick K, Javerzat J P
Institut de Biochimie et Génétique Cellulaires, Centre National de la Recherche Scientifique, Unité Propre de Recherche 9026, 33077 Bordeaux, Cedex, France.
J Cell Biol. 1998 Dec 28;143(7):1775-87. doi: 10.1083/jcb.143.7.1775.
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 Deltabub1 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.
纺锤体检验点通过延迟后期的发生，直到所有染色体都正确地附着在有丝分裂纺锤体上，从而确保染色体的正确分离。我们研究了裂殖酵母bub1基因在纺锤体检验点功能以及正常有丝分裂中的作用。我们发现，bub1(+)对于裂殖酵母纺锤体检验点对纺锤体损伤和着丝粒功能缺陷的反应至关重要。检验点的激活导致Bub1募集到着丝粒，并延迟有丝分裂的完成。我们表明，Bub1在正常的、未受干扰的有丝分裂中也起着关键作用。bub1功能的丧失会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Δbub1二倍体中更为明显，导致大量染色体错分离事件和二倍体状态的丧失，表明bub1(+)功能对于在有丝分裂过程中维持正确的倍性至关重要。与较大的真核生物一样，Bub1在有丝分裂早期被募集到动粒。然而，与其脊椎动物对应物不同的是，一部分Bub1在中期甚至直到末期都与着丝粒相关联。我们讨论了中期-后期转换后Bub1激酶发挥作用的可能性。
