The Mek1 phosphorylation cascade plays a role in meiotic recombination of Schizosaccharomyces pombe
The Mek1 phosphorylation cascade plays a role in meiotic recombination of Schizosaccharomyces pombe
复制标题
DOI：
10.4161/cc.9.23.14050
复制
发表时间：
2010-12
期刊：
影响因子：
4.3
通讯作者：
T. Tougan;Takashi Kasama;Ayami Ohtaka;D. Okuzaki;Takamune T. Saito;P. Russell;H. Nojima
中科院分区：
文献类型：
--
作者：
T. Tougan;Takashi Kasama;Ayami Ohtaka;D. Okuzaki;Takamune T. Saito;P. Russell;H. Nojima
Mek1是一种与Chk2/Rad53/ cds1相关的蛋白激酶，是pombe Schizosaccharomyces减数分裂正常进行所必需的。然而，Mek1调控的分子机制和Mek1磷酸化靶点尚不清楚。在这里，我们报道了Mek1在丝氨酸-12 （S12）、S14和苏氨酸-15 （T15）位点被Rad3 （ATR）和/或Tel1 （ATM）激酶磷酸化，这些激酶被减数分裂程序性双链断裂（dsb）激活。丙氨酸替代导致这些位点的突变导致减数分裂进程和重组率异常。这些位点的磷酸化触发Mek1的自磷酸化；事实上，Mek1激活环中Mek1- t318和-T322残基的丙氨酸替代突变降低了Mek1激酶活性和减数分裂重组率。Mek1的底物包括Mus81-T275、Rdh54-T6和Rdh54-T673。已知Mus81- t275调节Mus81在DNA切割中的功能，而Rdh54-T6A/T673A突变细胞表现出异常的减数分裂重组。综上所述，我们得出结论，Mek1的Rad3或Tel1磷酸化、Mek1的自磷酸化以及Mek1的Mus81或Rdh54磷酸化调节了pombe的减数分裂进程。
Mek1 is a Chk2/Rad53/Cds1-related protein kinase that is required for proper meiotic progression of Schizosaccharomyces pombe. However, the molecular mechanisms of Mek1 regulation and Mek1 phosphorylation targets are unclear. Here, we report that Mek1 is phosphorylated at serine-12 (S12), S14 and threonine-15 (T15) by Rad3 (ATR) and/or Tel1 (ATM) kinases that are activated by meiotic programmed double-strand breaks (DSBs). Mutations of these sites by alanine replacement caused abnormal meiotic progression and recombination rates. Phosphorylation of these sites triggers autophosphorylation of Mek1; indeed, alanine replacement mutations of Mek1-T318 and -T322 residues in the activation loop of Mek1 reduced Mek1 kinase activity and meiotic recombination rates. Substrates of Mek1 include Mus81-T275, Rdh54-T6 and Rdh54-T673. Mus81-T275 is known to regulate the Mus81 function in DNA cleavage, whereas Rdh54-T6A/T673A mutant cells showed abnormal meiotic recombination. Taken together, we conclude that the phosphorylation of Mek1 by Rad3 or Tel1, Mek1 autophosphorylation and Mus81 or Rdh54 phosphorylation by Mek1 regulate meiotic progression in S. pombe.