"The K. Marxianus Small Protein Modifier Sumo Enhances Stress Tolerance" by Yasaman Setayeshpour

Date Awarded

2020

Document Type

Thesis

Degree Name

Master of Science (M.Sc.)

Department

Biology

Advisor

Oliver Kerscher

Committee Member

Diane Shakes

Committee Member

Shanta Hinton

Abstract

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 test our hypothesis that SUMO and SUMO pathway components play a role 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. By utilizing Km, we aimed to I) establish whether sumoylation and the SSR play a role in stress tolerance of Km and II) identify specific SUMO pathway components involved in stress tolerance of Km. Our results reveal that Km displays a distinct SSR. Additionally, by cloning nine Km SUMO pathway genes and using CRISPR/Cas9 technology, we were able to replace Sc SUMO with its Km ortholog and found that this replacement enhances the resistance of Sc cells to oxidative stress.

DOI

http://dx.doi.org/10.21220/s2-adv6-6w41

Rights

© The Author

Included in

Biology Commons

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