Control of landmark events in meiosis by the CDK Cdc28 and the meiosis-specific kinase Ime2
Control of landmark events in meiosis by the CDK Cdc28 and the meiosis-specific kinase Ime2
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DOI：
10.1101/gad.1101503
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发表时间：
2003-06-15
影响因子：
10.5
通讯作者：
Herskowitz, I
中科院分区：
文献类型：
--
作者：
Benjamin, KR;Zhang, C;Herskowitz, I
减数分裂被认为需要蛋白激酶Ime2早期的DNA复制和细胞周期蛋白依赖性激酶Cdc28晚期的染色体分离。为了阐明这些激酶的作用，我们使用对化学抑制剂敏感的条件突变体早期和晚期抑制它们的活性。我们的研究表明Cdc28和Ime2在减数分裂的S期和M期都有重要作用。早期抑制类似物敏感的cdc28-as1阻断DNA复制，揭示了以前未检测到的Cdc28的作用。然而，Cdc28在有丝分裂细胞周期中的功能之一是Sic1的降解。后期添加抑制剂ime2-as1揭示了意想不到的作用ime2在启动和执行染色体分离。Ime2对M期的需要部分地通过其对关键减数分裂转录因子Ndt80的刺激来解释，Ndt80反过来又是高Cdc28活性所需要的。根据Ime2的后期作用，我们观察到其活性在M期增加，依赖于Cdc28和Ndt80。我们推测，减数分裂细胞分裂的几个独特的功能反映了Ime2和Cdc28之间的劳动分工和监管协调。
Meiosis is thought to require the protein kinase Ime2 early for DNA replication and the cyclin-dependent kinase Cdc28 late for chromosome segregation. To elucidate the roles of these kinases, we inhibited their activities early and late using conditional mutants that are sensitive to chemical inhibitors. Our studies reveal that both Cdc28 and Ime2 have critical roles in meiotic S phase and M phase. Early inhibition of analog-sensitive cdc28-as1 blocked DNA replication, revealing a previously undetected role for Cdc28. Yet Cdc28 was dispensable for one of its functions in the mitotic cell cycle, degradation of Sic1. Late addition of inhibitor to ime2-as1 revealed unexpected roles of Ime2 in the initiation and execution of chromosome segregation. The requirement of Ime2 for M phase is partially explained by its stimulation of the key meiotic transcription factor Ndt80, which is needed in turn for high Cdc28 activity. In accordance with a late role for Ime2, we observed an increase in its activity during M phase that depended on Cdc28 and Ndt80. We speculate that several unique features of the meiotic cell division reflect a division of labor and regulatory coordination between Ime2 and Cdc28.