DNA double-strand breaks (DSBs) are the most hazardous DNA lesions for genome integrity since they interrupt the DNA chain, generating risks of chromosomal rearrangements, mutations or loss-of -heterozygosities frequently seen in cancers. During meiosis, DSBs are programmed and their repair by homologous recombination (HR) is key to the production of normal euploid gametes, by promoting homolog pairing and crossovers. HR requires DNA synthesis to reconstitute the DNA degraded during DSB resection. Despite playing crucial roles in the outcome of DSB repair in both meiotic and somatic cells and being potentially mutagenic, this step is poorly characterized at the protein level but also how the extent of DNA synthesis is regulated and what are the consequences of its deregulation.

We are using genome-wide mapping of DNA synthesis at meiotic DSBs to study how excess DNA synthesis is prevented, how the length of repair-associated DNA synthesis is influenced by the extent of end resection and other cis and trans-acting factors. In addition to these population-based studies, we also developed the use of single molecule approaches, allowing us to visualize the distribution of DSB repair synthesis on whole chromosomes, but also at a very fine, nucleotide-resolution, level.

I will present our latest progress on these approaches, and what they can tell us about the fine mechanism of homologous recombination taking place during meiosis.