Date of Completion

Spring 5-1-2022

Thesis Advisor(s)

Dr. Kyle Hadden; Dr. Ashis Basu; Dr. Charles Giardina

Honors Major

Molecular and Cell Biology


Medicinal Chemistry and Pharmaceutics | Pharmaceutics and Drug Design


Translesion synthesis (TLS) is a cellular mechanism utilized by cancer cells to tolerate DNA damage caused by chemotherapeutics, like cisplatin, by replicating past unrepaired lesions. This increases the rate of mutations, which leads to the emergence of drug-resistant cancer cells. Preliminary studies have shown that disrupting the protein-protein interactions (PPI) in the TLS heteroprotein complex increases cells’ sensitivity to first-line genotoxic chemotherapy, illustrating how inhibiting TLS assembly and function can significantly increase cancer cell death. These results underscore the therapeutic potential of targeting TLS PPI. Our current work in this area is focusing on inhibitors capable of disrupting the Rev7/Rev3 TLS PPI. This study identified three promising inhibitors that disrupt the Rev7/Rev3 PPI with verification of TLS inhibition through biochemical and cellular studies. Future research can use optimize these inhibitors to develop a new class of anti-cancer agents that can enhance the efficacy of other drugs and treatments that exert their effects through DNA damage.