Unrestrained spindle elongation during recovery from spindle checkpoint activation in cdc15-2 cells results in mis-segregation of chromosomes.
Unrestrained spindle elongation during recovery from spindle checkpoint activation in cdc15-2 cells results in mis-segregation of chromosomes.
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DOI：
10.1091/mbc.e09-07-0637
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发表时间：
2010-07-15
影响因子：
3.3
通讯作者：
Yeong FM
中科院分区：
文献类型：
--
作者：
Chai CC;Teh EM;Yeong FM
CDC15-2细胞在NOC处理后的恢复过程中不能协调纺锤体的伸长和动粒捕获。这是由于CDC15-2细胞和野生型细胞未能积累Pds1p，表明在存在纺锤体损伤的情况下，细胞周期的及时进展和PDS1的正确表达是重要的。在酿酒酵母的正常中期，染色体由分裂细胞相对两极的纺锤体发出的微管在着丝点捕获。将复制的染色体保持在一起的粘附素和位于着丝点的微管的拉力之间的力量平衡导致了姐妹染色单体在染色体分离之前的双向。动粒-微管相互作用的缺失或姐妹染色单体间凝聚力的丧失会触发纺锤体检查点，从而阻止细胞在中期分裂。我们在这里报告了一个男性突变体cdc15-2，虽然在接触Noc时能够激活纺锤体组件检查点，但在从纺锤体检查点激活的恢复过程中错误分离了染色体。CDC15-2细胞在Noc中被滞留，尽管它们的Pds1p水平没有在野生型细胞中积累。遗传分析表明，MAD2Δcdc15-2和Δ2 cdc15-2双突变体的Pds1p水平均低于单突变体。突变体的染色体错误分离是由于纺锤体在存在独立染色体的情况下过早伸长，可能是由于失去了对纺锤体中区蛋白Slk19p和动蛋白Cin8p的适当控制。我们的数据表明，较慢的细胞分裂周期过渡速度可能导致Pds1p积累水平不足，从而影响从纺锤体组装检查点激活的恢复。
cdc15-2 cells failed to coordinate spindle elongation and kinetochore capture during recovery from Noc treatment. This was due to a failure in the cdc15-2 cells to accumulate Pds1p as well as in wild-type cells, indicating that timely progression through the cell cycle and proper expression of PDS1 is important in the presence of spindle damage. During normal metaphase in Saccharomyces cerevisiae, chromosomes are captured at the kinetochores by microtubules emanating from the spindle pole bodies at opposite poles of the dividing cell. The balance of forces between the cohesins holding the replicated chromosomes together and the pulling force from the microtubules at the kinetochores result in the biorientation of the sister chromatids before chromosome segregation. The absence of kinetochore–microtubule interactions or loss of cohesion between the sister chromatids triggers the spindle checkpoint which arrests cells in metaphase. We report here that an MEN mutant, cdc15-2, though competent in activating the spindle assembly checkpoint when exposed to Noc, mis-segregated chromosomes during recovery from spindle checkpoint activation. cdc15-2 cells arrested in Noc, although their Pds1p levels did not accumulate as well as in wild-type cells. Genetic analysis indicated that Pds1p levels are lower in a mad2Δ cdc15-2 and bub2Δ cdc15-2 double mutants compared with the single mutants. Chromosome mis-segregation in the mutant was due to premature spindle elongation in the presence of unattached chromosomes, likely through loss of proper control on spindle midzone protein Slk19p and kinesin protein, Cin8p. Our data indicate that a slower rate of transition through the cell division cycle can result in an inadequate level of Pds1p accumulation that can compromise recovery from spindle assembly checkpoint activation.
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影响因子：
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