Mechanistic insight into crossing over during mouse meiosis

SUMMARY Characteristics of heteroduplex DNA illuminate how strands exchange during homologous recombination, but mismatch correction can obscure them. To investigate recombination mechanisms, meiotic crossover products were analyzed at two hotspots in Msh2 –/– mice containing homologous chromosomes derived from inbred strains. Recombination frequencies were unchanged in the mutant, implying that MSH2-dependent recombination suppression does not occur at this level of diversity. However, a substantial fraction of crossover products retained heteroduplex DNA in the absence of MSH2, and some also had multiple switches between parental markers suggestive of MSH2-independent correction. Recombinants appeared to reflect a biased orientation of crossover resolution, possibly stemming from asymmetry at DNA ends established in earlier intermediates. Many crossover products showed no evidence of heteroduplex DNA, suggesting dismantling by D-loop migration. Unlike the complexity of crossovers in yeast, these two modifications of the original double-strand break repair model may be sufficient to explain most meiotic crossing over in mice.