MEIOREP · Interplay between the program of DNA replication and meiotic recombination

The control of genome duplication is critical for proper cell growth and proliferation. Errors in DNA synthesis and defects in genome maintenance have been linked to many human diseases such as cancer. In eukaryotes, replication initiates at sites located throughout the genome called origins, whose activation and distribution define the program of DNA replication. However, while changes in this pattern of replication have been observed in Xenopus and Drosophila during development, in differentiating mouse and human cells, and in a number of cancers, it remains unknown whether undergoing S phase with particular programs of origin selection has actual consequences on cellular function. Using the fission yeast Schizosaccharomyces pombe, an excellent model for studying cell cycle progression and DNA replication, we have investigated the impact of modifying origin usage on the process of meiosis. Our work indicates that origin selection is a major determinant for organizing meiotic recombination, providing the first evidence for functional consequences of genome-wide changes in the replication program. Taking advantage of the system that we have established, we propose to study the links between these two fundamental processes at both the population and single cell levels, focusing on the mechanisms that coordinate origin activity with the exchange of genetic material through meiotic recombination.