Non-cohesive roles of cohesin in meiotic prophase

Cohesin belongs to the structural maintenance of chromosome (SMC) protein complex family, which plays a key role in the organization and stability of the genomes of all living cells. It is best known for holding sister chromatids together during cell division, ensuring accurate distribution of chromosomes. However, cohesin also has additional, older, non-cohesive functions, which are conserved down to its bacterial origins it helps fold and organize the genome, affecting which genes are active or silent. Cornelia de Lange Syndrome (CdLS), a severe developmental disorder classified as a cohesinopathy, may serve to illustrate the medical importance of these functions. Children born with CdLS often exhibit growth retardation, limb abnormalities, characteristic facial features, and intellectual disability. In around 6070% of identified cases, the syndrome is caused by mutations in NIPBL/Scc2, a gene that regulates cohesin. These mutations typically do not disrupt chromosome segregation but rather impair non-cohesive functions affecting gene regulation during development. This project aims to understand how cohesin contributes to chromosome architecture in meiosis aside from cohesion. The meiotic process lies at the heart of sexual reproduction through the generation of haploid germ cells. Compared to vegetative cells, meiosis provides additional opportunities to observe chromosome mechanics due to the increased complexity of its specialized divisions. Early experiments show that, in addition to establishing cohesion, NIPBL/Scc2 is essential for maintaining the overall structure of chromosomes during the pairing stage of homologous chromosomes in meiosis. In the absence of Scc2, chromosomes lose their organized architecture despite sister chromatids remaining physically connected. This disorganization is reversible when Scc2 is restored, offering a rare opportunity to study chromosome disassembly and reassembly in living cells. The project uses yeast as a model system, allowing precise genetic manipulation, super-resolution microscopy, and genome-wide analyses to explore these dynamic processes. While the main focus is on understanding chromosome behavior during meiosis, the findings may help illuminate conserved mechanisms. Studying how cohesin regulates genome structure in yeast may create opportunities to better understand how similar processes functionor fail in higher eukaryotes, including plants and humans. By shedding light on cohesins dynamic and non-cohesive roles, this project contributes to a broader understanding of how genomes are physically and functionally organizedand what consequences may arise when this organization is disrupted.