DNA Damage during Meiosis Induces Chromatin Remodeling and Synaptonemal Complex Disassembly
DNA Damage during Meiosis Induces Chromatin Remodeling and Synaptonemal Complex Disassembly
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DOI：
10.1016/j.devcel.2011.01.015
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发表时间：
2011-03-15
影响因子：
11.8
通讯作者：
Zetka, Monique
中科院分区：
文献类型：
--
作者：
Couteau, Florence;Zetka, Monique
必须准确修复生殖系基因组的DNA损伤，以确保完整的遗传信息传递给下一代。减数分裂对DNA损伤反应(DDR)提出了挑战，因为它普遍需要改变染色体结构，从而影响DNA修复结果。我们报道了在线虫粗线期晚期，染色体轴上存在减数分裂DDR，导致染色质重塑、联会复合体解体和轴分离。轴成分HTP-3是获得H_2AacK5的胚系所必需的，H_2AacK5是一种对DNA损伤作出反应的轴特异性染色质标记。受辐射的野生型表现出依赖于乙酰基转移酶MYS-1/Tip60的H2AacK5的减少和轴的分离。H_2AacK5水平的恢复需要ATM-1激酶，并与再突触相关。我们认为，减数分裂DDR涉及染色体轴上的早期染色质重塑，以拆除结构，促进同源重组，并在粗线期退出之前促进基于非同源的有效修复。
DNA damage to the germline genome must be accurately repaired to ensure transmission of intact genetic information to following generations. Meiosis presents challenges to the DNA damage response (DDR) because it universally requires changes to chromosome structure that can affect DNA repair outcomes. We report the existence of a meiotic DDR at chromosome axes that results in chromatin remodeling, synaptonemal complex disassembly, and axis separation in response to irradiation at late pachytene stages in C. elegans. The axis component HTP-3 is required for germline acquisition of H2AacK5, an axis-specific chromatin mark that is DNA damage responsive. Irradiated wild-types show reduction of H2AacK5 and axis separation that are dependent on the acetyltransferase MYS-1/TIP60. Restoration of H2AacK5 levels requires ATM-1 kinase and correlates with resynapsis. We propose that the meiotic DDR involves early chromatin remodeling at chromosome axes to dismantle structures promoting interhomolog recombination and facilitate efficient nonhomolog-based repair before pachytene exit.