Spatiotemporal control of meiotic recombination

Our goal is to understand the mechanisms controlling the distribution of genetic recombination during meiosis—a specialised cell division responsible for genome haploidisation during gametogenesis. We recently demonstrated that meiotic DNA breaks (DSBs) are predisposed to form concertedly, spaced periodically in a manner that suggests DNA breakage happens on the surface of a macromolecular structure—which we hypothesise is an assembly of the evolutionarily conserved pro-DSB complex “RMM”. We now bring forward exciting chromosome-conformation and DSB-mapping data that support our contention. In general terms, we aim to test how localised changes in higher-order chromosome structure shape, and are shaped by, the process of recombination. First, we will characterise the topological conformations that arise around preferred sites of DSB formation. Second, we will determine how changes in patterns of DSB formation and chromosome structure are linked in space and time, and what are the regulators. Third, we will explore how spatiotemporal control of DSB formation influences downstream patterns of genetic recombination. Finally, we will seek to integrate our findings into a generalised model of spatiotemporal regulation in meiosis that we will use to both describe—and use to derive and test predictions about—how meiotic chromosome morphogenesis and recombination behave and are regulated.