Abstract
In most meiotic systems, recombination is essential to form connections between homologs that ensure their accurate segregation from one another. Meiotic recombination is initiated by DNA double-strand breaks that are repaired using the homologous chromosome as a template. Studies of recombination in budding yeast have led to a model in which most early repair intermediates are disassembled to produce noncrossovers. Selected repair events are stabilized so they can proceed to form double-Holliday junction (dHJ) intermediates, which are subsequently resolved into crossovers. This model is supported in yeast by physical isolation of recombination intermediates, but the extent to which it pertains to animals is unknown. We sought to test this model in Drosophila melanogaster by analyzing patterns of heteroduplex DNA (hDNA) in recombination products. Previous attempts to do this have relied on knocking out the canonical mismatch repair (MMR) pathway, but in both yeast and Drosophila the resulting recombination products are complex and difficult to interpret. We show that, in Drosophila, this complexity results from a secondary, short-patch MMR pathway that requires nucleotide excision repair. Knocking out both canonical and short-patch MMR reveals hDNA patterns that reveal that many noncrossovers arise after both ends of the break have engaged with the homolog. Patterns of hDNA in crossovers could be explained by biased resolution of a dHJ; however, considering the noncrossover and crossover results together suggests a model in which a two-end engagement intermediate with unligated HJs can be disassembled by a helicase to a produce noncrossover or nicked by a nuclease to produce a crossover. While some aspects of this model are similar to the model from budding yeast, production of both noncrossovers and crossovers from a single, late intermediate is a fundamental difference that has important implications for crossover control.
Highlights
Meiotic recombination is initiated by a DSB on one chromatid followed by repair using the homologous chromosome as a template, resulting in crossover (CO) or noncrossover (NCO) products [1]
We propose that the trans heteroduplex DNA (hDNA) in Xpc; Msh6 mutants comes either from either twoended synthesis-dependent strand annealing (SDSA) or a process we term ‘‘two-end engagement’’, wherein both ends of a break engage with the same homologous chromatid and are extended by synthesis but are not ligated to produce a double-Holliday junction (dHJ)
Concluding remarks Our analysis of Drosophila meiotic recombination after eliminating both canonical and short-patch mismatch repair (MMR) reveals that trans hDNA is frequent in NCOs and that MMR-independent gene conversion tracts are infrequent in COs
Summary
Meiotic recombination is initiated by a DSB on one chromatid followed by repair using the homologous chromosome as a template, resulting in crossover (CO) or noncrossover (NCO) products [1]. The ill-defined mechanisms that determine the number and distribution of crossovers, is thought to act prior to the bifurcation of CO and NCO pathways [2]. This model has been derived largely from studies in Saccharomyces cerevisiae, with strong support coming from the physical isolation of molecules with the properties expected of the key intermediates [3,4]. In the budding yeast model, NCOs arise from synthesis-dependent strand annealing (SDSA), with limited, if any, contribution from
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