The DSBSunrise project is investigating several molecular events required for the transfer of genetic material from one generation to the next during sexual reproduction. This is an evolutionarily conserved process. It occurs in most sexually reproducing species. The molecular events studied in this project take place during meiosis, the specialised cell division that ensures the formation of haploid gametes from diploid precursor germ cells.
During meiosis, two divisions occur to halve the chromosome content, and the first, the reductional division, is unique to meiotic cells as it ensures the segregation of the parental (maternal and paternal) homologous chromosomes. For accurate reductional segregation, the maternal and paternal homologues must recognise each other and be topologically linked. The links are established by reciprocal exchanges of DNA through homologous recombination between homologs.
Thus, meiotic cells induce a high frequency of homologous recombination events, such that each pair of homologs undergoes at least one reciprocal exchange or crossover. Homologous recombination during meiosis is a multistep process initiated by the formation of DNA double-strand breaks, followed by their repair using the homologous chromosome as a template.
Collectively, these molecular processes not only ensure the proper transmission of chromosomes to the next generation, but also determine genetic linkage and have long-term consequences for genome evolution by generating novel combinations of alleles, thus contributing to an increase in genetic diversity. Of note, somatic cells use homologous recombination to repair various types of DNA damage, but the meiotic cell is unique in that it has a machinery and associated processes to induce intentional DNA breaks in its genome. Several hundred DNA double-strand breaks are generated in each mouse or human meiotic cell. Tight control is required to ensure that each of these DNA breaks is repaired faithfully by homologous recombination, without errors that could lead to the transmission of genomic changes to the progeny.
The DSBSunrise project aims to investigate several features of DNA break formation in meiotic cells and how they are regulated. It will search for molecular components, address how DNA break sites are organised along chromosomes, how they interact with structural components of the repair mechanism and chromosome organisation, and provide fundamental insights into the complex process of meiotic chromosomal recombination.
