Mek1 stabilizes Hop1-Thr318 phosphorylation to promote interhomolog recombination and checkpoint responses during yeast meiosis.
Mek1 stabilizes Hop1-Thr318 phosphorylation to promote interhomolog recombination and checkpoint responses during yeast meiosis.
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DOI：
10.1093/nar/gks920
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发表时间：
2012-12
影响因子：
14.9
通讯作者：
Wang TF
中科院分区：
文献类型：
--
作者：
Chuang CN;Cheng YH;Wang TF
Red1、Hop1和MEK1是三种酵母减数分裂特异的染色体蛋白，它们支持减数分裂重组的同源间偏向。MEK1也是检验点中的一种效应性蛋白激酶，对异常的DNA和/或轴结构做出反应。MEK1的激活需要依赖于Red1的Hop1-Thr(T)318的磷酸化，这是由哺乳动物DNA损伤感受器激酶ATR和ATM的酵母同源物Mec1和Tel1介导的。鉴于MEK1-谷胱甘肽S转移酶(GST)的异位表达在缺乏Mec1/TEL1依赖的检查点功能的情况下促进IH重组，有人认为MEK1可能通过直接磷酸化参与重组检查点的靶标而在减数分裂过程中发挥双重作用。在此，我们报道了MEK1在稳定Mec1/Tel1介导的Hop1-T318磷酸化而不是蛋白磷酸酶4介导的去磷酸化中具有正反馈活性。我们的结果还表明，GST-MEK1或MEK1-GST进一步促进了Hop1-T318的磷酸化。MEK1的这种正反馈功能不依赖于MEK1的S激酶活性，而依赖于MEK1的S叉头相关结构域及其精氨酸51残基。精氨酸51直接介导MEK1-FHA与磷酸化的Hop1-T318的相互作用。我们认为，Hop1-MEK1的相互作用类似于Rad53-Dun1信号通路，是通过磷酸化的Rad53和Dun1-FHA相互作用介导的。
Red1, Hop1 and Mek1 are three yeast meiosis-specific chromosomal proteins that uphold the interhomolog (IH) bias of meiotic recombination. Mek1 is also an effector protein kinase in a checkpoint that responds to aberrant DNA and/or axis structure. The activation of Mek1 requires Red1-dependent Hop1-Thr(T)318 phosphorylation, which is mediated by Mec1 and Tel1, the yeast homologs of the mammalian DNA damage sensor kinases ATR and ATM. As the ectopic expression of Mek1-glutathione S-transferase (GST) was shown to promote IH recombination in the absence of Mec1/Tel1-dependent checkpoint function, it was proposed that Mek1 might play dual roles during meiosis by directly phosphorylating targets that are involved in the recombination checkpoint. Here, we report that Mek1 has a positive feedback activity in the stabilization of Mec1/Tel1-mediated Hop1-T318 phosphorylation against the dephosphorylation mediated by protein phosphatase 4. Our results also reveal that GST-Mek1 or Mek1-GST further increases Hop1-T318 phosphorylation. This positive feedback function of Mek1 is independent of Mek1’s kinase activity, but dependent on Mek1’s forkhead-associated (FHA) domain and its arginine 51 residue. Arginine 51 directly mediates the interaction of Mek1-FHA and phosphorylated Hop1-T318. We suggest that the Hop1–Mek1 interaction is similar to the Rad53-Dun1 signaling pathway, which is mediated through the interaction of phosphorylated Rad53 and Dun1-FHA.
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影响因子：
4.8
作者：
Chen, Sheng-hong;Smolka, Marcus B.;Zhou, Huilin
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Kleckner, N
DOI：
10.1083/jcb.200810055
发表时间：
2009-06-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Burgess RC;Lisby M;Altmannova V;Krejci L;Sung P;Rothstein R
通讯作者：
Rothstein R