Exonucleolytic resection, critical to repair double-strand breaks (DSBs) by recombination, is not well understood, particularly in mammalian meiosis. Here, we define structures of resected DSBs in mouse spermatocytes genome-wide at nucleotide resolution. Resection tracts averaged 1100 nt, but with substantial fine-scale heterogeneity at individual hot spots. Surprisingly, EXO1 is not the major 5′ → 3′ exonuclease, but the DSB-responsive kinase ATM proved a key regulator of both initiation and extension of resection. In wild type, apparent intermolecular recombination intermediates clustered near to but offset from DSB positions, consistent with joint molecules with incompletely invaded 3′ ends. Finally, we provide evidence for PRDM9-dependent chromatin remodeling leading to increased accessibility at recombination sites. Our findings give insight into the mechanisms of DSB processing and repair in meiotic chromatin.

中文翻译：

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小鼠减数分裂中DNA断裂过程的分子结构和机制。

对于通过重组修复双链断裂（DSB）至关重要的核酸外切切除术尚未得到很好的理解，尤其是在哺乳动物减数分裂中。在这里，我们在全基因组小鼠精子细胞中以核苷酸分辨率定义了切除的DSBs的结构。切除道平均为1100 nt，但在各个热点处具有明显的细尺度异质性。出乎意料的是，EXO1不是主要的5'→3'核酸外切酶，但DSB反应激酶ATM证明了切除起始和扩展的关键调节因子。在野生型中，明显的分子间重组中间体聚集在DSB位置附近但与DSB位置偏离，这与具有不完全侵入3'末端的关节分子一致。最后，我们为依赖PRDM9的染色质重塑提供了证据，从而导致重组位点的可及性增加。