PhD defence M. (Macarena) Moronta Gines

Below is a brief summary of the dissertation:

How our DNA is organized inside cells is essential for life. Although every cell in our body contains the same genetic information, different cells use different parts of this information. A protein complex called cohesin plays an important role in organizing DNA and controlling which genes are active. When cohesin does not function properly, it can cause developmental disorders and contribute to disease.

In this thesis, I investigated how different versions of cohesin contribute to normal cell function and what happens when these proteins are disrupted. I focused on the STAG family of cohesin proteins, which help determine how cohesin organizes DNA. I discovered that closely related STAG proteins have both shared and specialized functions, allowing cells to maintain proper genome organization.

I also studied genetic changes affecting cohesin-associated proteins in patients with rare developmental disorders. These studies revealed new mechanisms that explain how changes in cohesin can lead to disease, including Cornelia de Lange syndrome and Mullegama-Klein-Martinez syndrome. Importantly, my research shows that cells have unexpected ways to compensate when one cohesin component is missing, by adapting the use of related proteins.

Together, these findings improve our understanding of how the organization of DNA influences human health and disease. This knowledge contributes to better interpretation of genetic variants found in patients and provides new insights into the biology underlying rare developmental disorders.