Date of Award
Fall 2025
Project Type
Thesis
Program or Major
Genetics
Degree Name
Master of Science
First Advisor
Konstantinos Sousounis
Second Advisor
Vicki Jeffers
Third Advisor
Sherine Elsawa
Abstract
Unlike humans, highly regenerative organisms such as salamanders encounter several genotoxic threats from repeated cycles of proliferation, resulting in DNA damage. Understanding the mechanisms by which these organisms resolve DNA damage to maintain genomic integrity during regeneration remains poorly understood. This research evaluated the roles of Eya2, Chk1, and Chk2 in the DNA damage response (DDR) during lens regeneration in the newt, Pleurodeles waltl. Pharmacological inhibitors were used to impair Eya2 and Chk1/2 function throughout regeneration. DNA damage, downstream cell cycle regulators, and proliferation markers were evaluated through histological and western blot analyses. Eya2 inhibition significantly reduces eye and regenerated lens size, increases p-Y142-H2AX, dysregulates CCNB1 and p-Chk1, and subsequently reduces S-phase entry. Conversely, Chk1/2 inhibition reduced eye size, but did not disrupt lens regeneration. p-JNK levels were notably reduced, suggesting a possible interplay in the DDR. Overall, Eya2 was found to be a key regulator of DNA damage and cell cycle progression during regeneration across tissue types and multiple salamander species. These results shed light on the significance of the DDR in regenerative organisms as it may inform future therapies for chronic ocular disease.
Recommended Citation
Ahearn, Kelsey Elise, "FUNCTIONS OF DNA DAMAGE RESPONSE PROTEINS EYA2 AND CHECKPOINT KINASES 1&2 DURING LENS REGENERATION IN PLEURODELES WALTL" (2025). Master's Theses and Capstones. 2022.
https://scholars.unh.edu/thesis/2022