姐妹染色单体分离和染色体再复制受不同机制调控，以应对纺锤体损伤。
Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage.
作者信息
Alexandru G, Zachariae W, Schleiffer A, Nasmyth K
机构信息
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
出版信息
EMBO J. 1999 May 17;18(10):2707-21. doi: 10.1093/emboj/18.10.2707.
Abstract
In yeast, anaphase entry depends on Pds1 proteolysis, while chromosome re-duplication in the subsequent S-phase involves degradation of mitotic cyclins such as Clb2. Sequential proteolysis of Pds1 and mitotic cyclins is mediated by the anaphase-promoting complex (APC). Lagging chromosomes or spindle damage are detected by surveillance mechanisms (checkpoints) which block anaphase onset, cytokinesis and DNA re-replication. Until now, the MAD and BUB genes implicated in this regulation were thought to function in a single pathway that blocks APC activity. We show that spindle damage blocks sister chromatid separation solely by inhibiting APCCdc20-dependent Pds1 proteolysis and that this process requires Mad2. Blocking APCCdh1-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different protein, Bub2. Our data imply that Mad1, Mad2, Mad3 and Bub1 regulate APCCdc20, whereas Bub2 regulates APCCdh1.
摘要
在酵母中，后期进入依赖于Pds1的蛋白水解作用，而在随后的S期染色体重新复制涉及有丝分裂周期蛋白（如Clb2）的降解。Pds1和有丝分裂周期蛋白的顺序蛋白水解作用由后期促进复合物（APC）介导。滞后染色体或纺锤体损伤通过监测机制（检查点）检测，这些机制会阻止后期开始、胞质分裂和DNA重新复制。到目前为止，参与这种调节的MAD和BUB基因被认为在一个阻止APC活性的单一途径中发挥作用。我们发现纺锤体损伤仅通过抑制APCCdc20依赖的Pds1蛋白水解作用来阻止姐妹染色单体分离，并且这个过程需要Mad2。阻止APCCdh1介导的Clb2蛋白水解作用和染色体重新复制不需要Mad2，而是需要一种不同的蛋白质Bub2。我们的数据表明，Mad1、Mad2、Mad3和Bub1调节APCCdc20，而Bub2调节APCCdh1。
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本文引用的文献
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Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14.细胞周期后期促进复合物（APC）调节因子Hct1的抑制性磷酸化由激酶Cdc28和磷酸酶Cdc14控制。
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