Yasaman Setayeshpour

SUMO, a small ubiquitin-like modifier protein, becomes attached to specific eukaryotic proteins to modulate their function and activity. The importance of SUMO modification in cell cycle progression, transcriptional regulation, and DNA damage-related processes has been firmly established. In contrast, a SUMO-dependent Stress Response (SSR) exists, but this process remains ill-defined. When cells are exposed to proteotoxic and genotoxic stressors, the SSR involves a rapid and dramatic increase in SUMO-modified proteins. The SSR is believed to play a cytoprotective role for normal cells, but it may also enhance the robustness of cancerous cells and eukaryotic pathogens. To investigate the role that SUMO and SUMO pathway components play in stress tolerance, we utilize the stress tolerant yeast Kluyveromyces marxianus (Km). Unlike Saccharomyces cerevisiae (Sc) cells, Km cells thrive at temperatures of up to 49°C and are highly resistant to oxidative stress and UV irradiation. We have cloned nine genes of the SUMO pathway from the stress-tolerant Km to determine their contribution to stress tolerance. Using CRISPR/Cas9 technology, we are replacing these Sc SUMO pathway genes at their corresponding Km orthologs. Results from our experiments reveal that replacements of some Sc SUMO pathway genes with their Km orthologs enhances Sc cell resistance to oxidative stress and DNA damage. Ultimately, we seek to understand how adaptive genetic variations in SUMO pathway genes promote stress resilience.

Yasaman Setayeshpour is a second-year M.S. candidate in the Biology Department at William & Mary. She has a broad interest in the study of functional consequences due to genetic variants. She is currently investigating the involvement of certain proteins in stress tolerance in yeast.