The Base Excision Repair (BER) machinery has evolved to process DNA bases damaged by reactive oxygen and nitrogen species as well as base lesions induced by alkylating agents. Deficient repair of damaged bases results in mutagenesis and genomic instability, whereas efficient repair of alkylating agents used to treat tumors leads to drug resistance. Human genome sequencing studies show that there are hundreds of germline variants in BER genes that are likely to encode proteins with altered function. This presentation will focus on the mechanistic insights gained from our characterization of some of these germline BER variants. We have discovered that variants in DNA glycosylase and DNA polymerase genes induce genomic instability and cellular transformation when expressed in non-transformed cells. These phenotypes result from defective or aberrant enzymatic function. Our results suggest that germline variants of BER genes likely increase risk for cancer and other diseases.
Citation Format: Joann B. Sweasy. Base excision repair and cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-005.