Project Details
Projekt
„Regulation of crossover formation across sister pairs”
Applicant
Dr. Simone Köhler
Subject Area
Cell Biology
General Genetics and Functional Genome Biology
General Genetics and Functional Genome Biology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 573289788
Meiosis is essential for generating diverse gametes for sexual reproduction. A key feature of this process is crossover (CO) formation between homologous chromosomes, which must be closely regulated to safeguard genome integrity for future generations. Meiotic COs are regulated by at least two mechanisms: CO assurance, which ensures that at least one CO is formed per homologous chromosome pair, and CO interference, which spaces COs far apart from one another. These mechanisms typically act across entire chromosomes. However, since each CO involves only two of the four chromatids in a homologous chromosome pair, additional mechanisms may regulate which chromatids participate in CO formation when multiple COs are formed. Understanding this "chromatid interference" could reveal new layers of regulation beyond the traditional chromosome-wide control of CO formation. Our recent work in C. elegans has provided an unexpected insight into chromatid-specific CO regulation: Mutations in the disordered C-terminal domain of SYP-4, a component of the synaptonemal complex (SC), disrupt chromosome-wide CO regulation, eliminating CO interference or both CO assurance and interference. However, these mutations retain a non-random distribution of COs between sister chromatids, suggesting a separate mechanism for selecting chromatids for CO formation. This raises the question of how sister chromatids are selected for recombination when global CO regulation fails. To address this question, we will investigate the molecular and structural mechanisms that govern sister chromatid selection during CO formation in C. elegans. Prior evidence and our preliminary data suggest that processes like double strand break (DSB) formation, the molecular organization of recombination intermediates, and/or a biased resolution may influence which chromatids participate in CO formation. We will combine genetic epistasis experiments, high- and super-resolution microscopy, and biochemical experiments to investigate the mechanisms underlying chromatid-specific regulation. Importantly, misregulated COs can disrupt chromosome reorganization and joint molecule resolution, potentially leading to missegregation during the meiotic divisions. By analyzing chromosome segregation in mutants with altered chromatid selection, we will determine whether the incorrect distribution of COs increases the risk of meiotic errors. This project will provide a detailed understanding of the mechanisms that govern sister chromatid selection during meiosis. Our project could uncover new layers of CO regulation and offer new insights into the general principles of recombination and its role in maintaining genome stability across generations.
DFG Programme
Research Grants
International Connection
Austria
