View Program - 63rd Annual Drosophila Research Conference

Meiosis is a specialized form of cell division that generates haploid gametes from diploid cells. Crossovers between homologous chromosomes are essential to accurate chromosome segregation during meiosis, and chromosome missegregation leads to miscarriage and chromosomal disorders such as Down syndrome. Crossovers are generated via homologous recombination, a process that repairs double-strand DNA breaks (DSBs) using a homologous template. Many more breaks than crossovers are formed, and the number and position of crossovers are highly regulated in a phenomenon termed "crossover patterning." Despite crossover patterning's discovery over a century ago, the mechanisms that govern it remain unclear. A classical model for homologous recombination suggests that all crossovers are derived from a single symmetrical intermediate, with noncrossover products being derived from an earlier intermediate. The multiple pathways within homologous recombination can be traced via heteroduplex DNA (hDNA), DNA in which the strands are derived from different parent molecules (e.g. homologous chromosomes). Normally, SNPs and indels between the strands in hDNA are repaired by mismatch repair to form gene conversions or restorations of the original sequence. Our lab has found that Drosophila Xpc ; Msh6 mutants, deficient in both canonical and short-patch mismatch repair, exhibit continuous hDNA tracts, making Drosophila the only metazoan thus far in which this has been achievable. Our lab has studied these hDNA tracts at a test locus and found hDNA signatures conflicting with the classical recombination model. However, much more extensive analysis than is possible at this test locus is required to revise this model. I am conducting whole-genome sequencing of hDNA to determine if the signatures seen at a single locus are consistent genome-wide, and whether certain hDNA signatures are localized to specific regions of the genome. This analysis will shed light on meiotic recombination mechanism and will inform if and how pathway choices in recombination differ in different genomic contexts. Understanding meiotic recombination mechanism and pathway choice is crucial to determining its connection to crossover patterning and proper homolog segregation.

Mechanisms and regulation of meiotic recombination: a whole-genome approach