We aim to uncover the molecular mechanisms that enable heredity and immortality in the germline. Our main focus is on how germ cells ensure safe and accurate transmission of genome information during meiosis. Paradoxically, genome maintenance requires programmed generation of large numbers of DNA breaks in meiosis. These DNA breaks initiate a modified homologous recombination process that pairs homologous chromosomes, and generates crossing overs between them. These crossing overs both enable correct meiotic chromosome segregation and create new allele combinations for evolution to act on. Orderly crossing over formation and the prevention of fatal genome damage from DNA breaks critically depend on unique meiotic features in cell cycle and chromosome biology. To uncover the underlying cellular and molecular mechanisms, we have been identifying previously uncharacterized genes/proteins that play crucial roles in meiosis. We have used cytogenetics, biochemistry, chromatin analysis and transcriptomics for the functional analysis of our newly identified meiotic factors. Thereby, we have both uncovered previously unappreciated meiotic processes and also gained novel insights into long-standing questions of meiotic chromosome biology.
Key questions addressed by our flagship projects include:
1. How do meiotic checkpoints enable quality control of meiotic recombination and the pairing of homologous chromosomes?
2. How do meiocytes control DNA break formation?
3. How do meiocytes ensure that DNA break repair is efficient and that it results in crossing overs between homologous chromosomes?
4. How do meiosis-specific chromatin structures, e.g. the meiotic chromosome axis and the synaptonemal complex, enable meiotic recombination and its quality control?
5. What are the unique principles of meiotic chromatin organization that permits parallel implementation of meiotic transcription and recombination mediated DNA repair?