Continuous double-strand break induction and their differential processing sustain chiasma formation during Caenorhabditis elegans meiosis
Continuous double-strand break induction and their differential processing sustain chiasma formation during Caenorhabditis elegans meiosis
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DOI：
10.1016/j.celrep.2022.111403
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发表时间：
2022-09-27
期刊：
影响因子：
8.8
通讯作者：
Silva，Nicola
中科院分区：
文献类型：
--
作者：
Hicks，Tara;Trivedi，Shalini;Silva，Nicola
染色体可靠地分离到配子中取决于Spo 11诱导的DNA双链断裂（DSB）。这些在切除后产生单链3′尾以促进交叉（CO）。虽然早期Mre 11依赖的末端切除是大多数生物体中的主要途径，但Exo 1或Dna 2/BLM也有助于减数分裂DSB的有效加工。虽然它的酶活性已被彻底解剖，Spo 11活动的时间动力学基本上仍然难以捉摸。我们发现，在秀丽隐杆线虫，SPO-11介导的DSB诱导发生在整个早期减数分裂前期I，直到中后期粗线。我们发现，后期DSBs是必不可少的CO的形成，并优先处理EXO-1和DNA-2的冗余方式。此外，EXO-1-DNA-2介导的切除确保完成保守的DSB修复并阻止KU依赖性末端连接的激活。总之，我们的数据揭示了DSB诱导的重要时间方面，并确定了以前未知的EXO-1-DNA-2介导的切除活性在秀丽隐杆线虫中的功能意义。
Faithful chromosome segregation into gametes depends on Spo11-induced DNA double-strand breaks (DSBs). These yield single-stranded 3′ tails upon resection to promote crossovers (COs). While early Mre11-dependent end resection is the predominant pathway in most organisms, Exo1 or Dna2/BLM can also contribute to the efficient processing of meiotic DSBs. Although its enzymatic activity has been thoroughly dissected, the temporal dynamics underlying Spo11 activity have remained mostly elusive. We show that, inCaenorhabditis elegans, SPO-11-mediated DSB induction takes place throughout early meiotic prophase I until mid-late pachynema. We find that late DSBs are essential for CO formation and are preferentially processed by EXO-1 and DNA-2 in a redundant fashion. Further, EXO-1-DNA-2-mediated resection ensures completion of conservative DSB repair and discourages activation of KU-dependent end joining. Taken together, our data unveil important temporal aspects of DSB induction and identify previously unknown functional implications for EXO-1-DNA-2-mediated resection activity inC. elegans.