Curriculum in Genetics and Molecular Biology, 120 Mason Farm Road, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Pediatrics, Division of Medical Genetics, University of Washington, Seattle, Washington and Seattle Children's Hospital, Seattle, WA 98105, USA.
Nucleic Acids Res. 2021 Jan 25;49(2):879-890. doi: 10.1093/nar/gkaa1205.
Programmed DNA double-strand breaks (DSBs) made during meiosis are repaired by recombination with the homologous chromosome to generate, at selected sites, reciprocal crossovers that are critical for the proper separation of homologs in the first meiotic division. Backup repair processes can compensate when the normal meiotic recombination processes are non-functional. We describe a novel backup repair mechanism that occurs when the homologous chromosome is not available in Drosophila melanogaster meiosis. In the presence of a previously described mutation (Mcm5A7) that disrupts chromosome pairing, DSB repair is initiated by homologous recombination but is completed by non-homologous end joining (NHEJ). Remarkably, this process yields precise repair products. Our results provide support for a recombination intermediate recently proposed in mouse meiosis, in which an oligonucleotide bound to the Spo11 protein that catalyzes DSB formation remains bound after resection. We propose that this oligonucleotide functions as a primer for fill-in synthesis to allow scarless repair by NHEJ. We argue that this is a conserved repair mechanism that is likely to be invoked to overcome occasional challenges in normal meiosis.
程序性 DNA 双链断裂（DSBs）在减数分裂期间形成，通过与同源染色体的重组修复，在选定的位点产生相互易位，这对于第一次减数分裂中同源染色体的正确分离至关重要。当正常的减数重组过程不起作用时，备份修复过程可以进行补偿。我们描述了一种在果蝇减数分裂中同源染色体不可用时发生的新型备份修复机制。在先前描述的突变（Mcm5A7）存在的情况下，该突变破坏了染色体配对，DSB 的修复是由同源重组起始的，但由非同源末端连接（NHEJ）完成。值得注意的是，这个过程产生了精确的修复产物。我们的结果为最近在小鼠减数分裂中提出的重组中间产物提供了支持，其中与 Spo11 蛋白结合的催化 DSB 形成的寡核苷酸在切除后仍保持结合。我们提出，这个寡核苷酸可以作为填充合成的引物，允许通过 NHEJ 进行无疤痕修复。我们认为，这是一种保守的修复机制，可能会被调用以克服正常减数分裂中的偶尔挑战。
