Cellular Repair of Synthetic Analogs of Oxidative DNA Damage Reveals a Key Structure-Activity Relationship of the Cancer-Associated MUTYH DNA Repair Glycosylase.

ABSTRACT: The base excision repair glycosylase MUTYH prevents mutations associated with the oxidatively damaged base, 8-oxo-7,8-dihydroguanine (OG), by removing undamaged misincorporated adenines from OG:A mispairs. Defects in OG:A repair in individuals with inherited MUTYH variants are correlated with the colorectal cancer predisposition syndrome known as MUTYH-associated polyposis (MAP). Herein, we reveal key structural features of OG required for efficient repair by human MUTYH using structure-activity relationships (SAR). We developed a GFP-based plasmid reporter assay to define SAR with synthetically generated OG analogs in human cell lines. Cellular repair results were compared with kinetic parameters measured by adenine glycosylase assays in vitro. Our results show substr

SUBMITTER: Conlon SG 

PROVIDER: S-EPMC10906249 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature