Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation.
Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation.
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DOI：
10.1016/j.molcel.2009.09.029
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发表时间：
2009-11-13
期刊：
影响因子：
16
通讯作者：
Hollingsworth, Nancy M.
中科院分区：
文献类型：
--
作者：
Niu, Hengyao;Wan, Lihong;Busygina, Valeria;Kwon, YoungHo;Allen, Jasmina A.;Li, Xue;Kunz, Ryan C.;Kubota, Kazuishi;Wang, Beatrice;Sung, Patrick;Shokat, Kevan M.;Gygi, Steven P.;Hollingsworth, Nancy M.
在同源重组中，对同源染色单体的偏好是减数分裂细胞和有丝分裂细胞的根本区别。在芽殖酵母中，在减数分裂中对同源重组的偏向需要Dmc1重组酶和减数分裂特异的激酶MEK1，MEK1抑制有丝分裂重组酶RAD51与姐妹染色单体的接触。在这里，蛋白质组学、生化和遗传学方法的结合已经确定MEK1通过其结合伙伴Rad54的磷酸化来抑制RAD51重组酶的活性。苏氨酸132的RAD54磷酸化减少了与RAD51的复合体的形成，该位置的负电荷在体外和体内都降低了RAD51的功能。因此，MEK1的磷酸化通过两种方式提供了一种控制重组伙伴选择的动态手段：(1)它通过抑制RAD51/Rad54复合体的形成来降低RAD51的活性；(2)它通过一种不依赖于Rad54的机制来抑制RAD51介导的姐妹染色单体的链侵袭。
A preference for homologs over sister chromatids in homologous recombination is a fundamental difference in meiotic versus mitotic cells. In budding yeast, the bias for interhomolog recombination in meiosis requires the Dmc1 recombinase and the meiosis-specific kinase, Mek1, which suppresses engagement of sister chromatids by the mitotic recombinase, Rad51. Here, a combination of proteomic, biochemical and genetic approaches has identified an additional role for Mek1 in inhibiting the activity of the Rad51 recombinase through phosphorylation of its binding partner, Rad54. Rad54 phosphorylation of threonine 132 attenuates complex formation with Rad51 and a negative charge at this position reduces Rad51 function in vitro and in vivo. Thus, Mek1 phosphorylation provides a dynamic means of controlling recombination partner choice in meiosis in two ways: (1) it reduces Rad51 activity through inhibition of Rad51/Rad54 complex formation and (2) it suppresses Rad51-mediated strand invasion of sister chromatids via a Rad54-independent mechanism.
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