Cohesin, a ring-shaped protein complex, is crucial for genome stability, gene expression, sister chromatid cohesion, and DNA repair. It forms intrachromosomal loops during interphase, aiding in chromatin organization by bringing enhancers and promoters together. Cohesin also ensures sister chromatid cohesion during DNA replication and repairs double-strand breaks (DSBs). In response to DNA damage, cohesin binds to DSBs and enhances cohesion via damage-induced cohesion (DI-cohesion). Our recent findings show that cohesin tethers DSB ends through oligomer formation (Phipps et al., 2025).
This research project aims, in the frame of an ANR funded project, to explore how DNA damage influences cohesin’s functions in genome stability. The main hypothesis is that DNA damage activates distinct cohesin populations with specific roles critical for maintaining genome integrity. Using Saccharomyces cerevisiae as a model, the project focuses on three goals: analyzing the impact of DNA damage on cohesin composition and modifications, studying oligomerization in DSB tethering, and identifying the cohesin populations involved in DI-cohesion.
The methodology combines biochemical, genetic, and genomic approaches. Key tasks include identifying new cohesin interactors, analyzing cohesin in specific mutants, and investigating post-translational modifications.
This project aims to provide comprehensive insights into cohesin’s diverse roles in genome stability beyond traditional sister chromatid cohesion.