Elevated Rad53 kinase activity influences formation and interhomolog repair of meiotic DNA double-strand breaks in budding yeast.
Elevated Rad53 kinase activity influences formation and interhomolog repair of meiotic DNA double-strand breaks in budding yeast.
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Rad53 激酶活性升高会影响芽殖酵母中减数分裂 DNA 双链断裂的形成和同源修复。
DOI：
10.1016/j.bbrc.2013.10.111
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kanehara Y.
中科院分区：
文献类型：
--
作者：
Usui T.;Kanehara Y.
减数分裂细胞产生生理程序性DNA双链断裂（DSB）以启动减数分裂重组。通过减数分裂重组进行的程序化DSB的同源物间修复对于确保减数分裂I时染色体的准确分离以产生正常配子至关重要。在芽殖酵母中，DNA损伤检查点激酶Rad 53被有丝分裂和减数分裂中意外发生的DNA损伤DSB激活;然而，发生在每个基因组约160个基因座处的减数分裂程序化DSB未能激活激酶。因此，Rad 53的激活似乎是沉默的减数分裂程序DSB。在这项研究中，为了解决Rad 53对减数分裂DSB不敏感的生物学意义，我们研究了Rad 53过表达对减数分裂过程的影响。过表达导致Rad 53的部分激活，揭示了Rad 53激酶激活对减数分裂进程以及减数分裂程序性DSB的形成和同源物间修复的负面影响。
Meiotic cells generate physiological programmed DNA double-strand breaks (DSBs) to initiate meiotic recombination. Interhomolog repair of the programmed DSBs by meiotic recombination is vital to ensure accurate chromosome segregation at meiosis I to produce normal gametes. In budding yeast, the DNA damage checkpoint kinase Rad53 is activated by DSBs which accidentally occur as DNA lesions in mitosis and meiosis; however, meiotic programmed DSBs which occur at ∼160 loci per genome fail to activate the kinase. Thus, Rad53 activation appears to be silenced in response to meiotic programmed DSBs. In this study, to address the biological significance of Rad53’s insensitivity to meiotic DSBs, we examined the effects of Rad53 overexpression on meiotic processes. The overexpression led to partial activation of Rad53, uncovering that the negative impacts of Rad53 kinase activation on meiotic progression, and formation and interhomolog repair of meiotic programmed DSBs.