Date of Award
2025
Document Type
Honors Thesis (Colby Access Only)
Department
Colby College. Biology Dept.
Advisor(s)
Yee Mon Thu
Second Advisor
Robert C. Augustine
Third Advisor
Andrea R. Tilden
Abstract
SUMOylation is a post-translational modification process that is vital in regulating cellular response to replication stress. Particularly, the E3 SUMO ligases are important for conferring substrate specificity. The budding yeast E3 SUMO ligase Mms21 and its human homolog Nsmce2 are well understood to promote repair of DNA damage and prevent genomic instability in response to replication stress induced by genotoxic chemicals. However, the role and mechanism of Mms21 in responding to replication stress caused by oncogenes is not well understood. Oncogenic overexpression of G1/S cyclins disrupts G1 phase origin licensing and leads to replication stress, genomic instability, and tumour development. Here, we investigated the role of Mms21’s SUMO ligase activity in mitigating oncogenic G1/S Cln2 cyclin overexpression-induced replication stress in budding yeast. We show that Mms21 ligase activity reduces the growth defect resulting from overexpression of Cln2. Our finding suggests that Mms21 can potentially reduce oncogenic replication stress. Our study highlights the utility of yeast as a genetic model for human cancers and the necessity to further study how Mms21 SUMOylation defends cells against cancer.
Keywords
SUMO, budding yeast, human cancers, replication stress, cyclin dysregulation, genome instability
Recommended Citation
Li, Cheung, "The Role of Mms21 SUMOylation in Responding to Oncogenic Cln2 Overexpression-induced Replication Stress in Budding Yeast" (2025). Honors Theses. Paper 1507.https://digitalcommons.colby.edu/honorstheses/1507
