Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination
Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination
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DOI：
10.1101/gad.1626608
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发表时间：
2008-02-01
影响因子：
10.5
通讯作者：
Ohta, Kunihiro
中科院分区：
文献类型：
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作者：
Sasanuma, Hiroyuki;Hirota, Kouji;Ohta, Kunihiro
减数分裂确保配子和有性生殖的遗传多样性。对于成功的减数分裂，多个事件，如DNA复制，重组和染色体分离必须协调发生在一个严格的调控秩序。我们研究了Cdc 7激酶在减数分裂重组启动中的作用，即Spo 11和其他共激活蛋白介导的DNA双链断裂（DSB）。使用bob 1 -1 cdc 7 Delta的遗传分析表明，Cdc 7是减数分裂DSB和减数分裂I进程所必需的。我们还表明，Mer 2，一个Spo 11辅助蛋白所需的DSB形成和磷酸化的细胞周期蛋白依赖性激酶（CDK）的N-末端区域，包含两种类型的Cdc 7依赖性磷酸化位点附近的CDK网站（Ser 30）：一个（Ser 29）是必不可少的减数分裂DSB的形成，和其他表现出累积效应，以促进DSB的形成。重要的是，这些位点上的突变赋予DSB形成严重缺陷，即使当CDK磷酸化存在于Ser 30时。cdc 7 δ的二倍体不仅在Spo 11的染色质结合中显示缺陷，而且在Rec 114和Mei 4的染色质结合中也显示缺陷，Rec 114和Mei 4是可能有助于Spo 11与DSB热点结合的其他减数分裂共激活因子。因此，我们建议，Cdc 7，与CDK，调节Spo 11加载DSB网站通过Mer 2磷酸化。
Meiosis ensures genetic diversification of gametes and sexual reproduction. For successful meiosis, multiple events such as DNA replication, recombination, and chromosome segregation must occur coordinately in a strict regulated order. We investigated the meiotic roles of Cdc7 kinase in the initiation of meiotic recombination, namely, DNA double-strand breaks (DSBs) mediated by Spo11 and other coactivating proteins. Genetic analysis using bob1-1 cdc7 Delta reveals that Cdc7 is essential for meiotic DSBs and meiosis I progression. We also demonstrate that the N-terminal region of Mer2, a Spo11 ancillary protein required for DSB formation and phosphorylated by cyclin-dependent kinase (CDK), contains two types of Cdc7-dependent phosphorylation sites near the CDK site (Ser30): One (Ser29) is essential for meiotic DSB formation, and the others exhibit a cumulative effect to facilitate DSB formation. Importantly, mutations on these sites confer severe defects in DSB formation even when the CDK phosphorylation is present at Ser30. Diploids of cdc7 Delta display defects in the chromatin binding of not only Spo11 but also Rec114 and Mei4, other meiotic coactivators that may assist Spo11 binding to DSB hot spots. We thus propose that Cdc7, in concert with CDK, regulates Spo11 loading to DSB sites via Mer2 phosphorylation.