Turcotte, C. A. | Search bioRxiv

bioRxiv2026

Chromosome-specific differences in the recombination landscape of spontaneous meiotic nondisjunction

Failures in chromosome segregation during meiosis result in aneuploid gametes and are the leading cause of miscarriage. The position and number of crossovers, genetic exchanges between homologous chromosomes, are essential to their accurate disjunction in meiosis. Previous research analyzing nondisjunction of acro- and telocentric chromosomes in human and Drosophila has identified altered positioning and number of crossovers that differs between meiosis I and meiosis II nondisjunction. Limited data from positioning in chromosomes that segregated normally in metacentric trisomies has suggested discrepancies between the behavior of these chromosomes and the acro/telocentrics in nondisjunction, which warrants further investigation. Here, we employ whole-genome sequencing to study spontaneous meiotic nondisjunction of the metacentric chromosome 2 in Drosophila melanogaster. Several patterns of recombination may differentially impact telo- versus metacentric chromosomes: lack of a crossover, distal crossovers, and proximal crossovers. We find that unlike meiotic nondisjunction of the Drosophila X chromosome, nondisjunction of chromosome 2 is not associated with dramatic changes in crossover landscape, but is associated with reduced recombination. Differences in the proportions of NDJ events with altered recombination patterns between chromosomes X and 2 suggest that abnormal crossover positions disparately affect chromosomes with different shapes. Taken together, these findings highlight that the underlying triggers of meiotic nondisjunction are chromosome-specific.

genetics↗

bioRxiv2020

Collaboration between homologous recombination and non-homologous end joining in repair of meiotic double-strand breaks in Drosophila

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 divisions. 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 discovered 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.

genetics↗