A Germline Polymorphism of DNA Polymerase Beta Induces Genomic Instability and Cellular Transformation

摘要: Several germline single nucleotide polymorphisms (SNPs) have been identified in the POLB gene, but little is known about their cellular and biochemical impact. DNA Polymerase β (Pol β), encoded by main gap-filling polymerase involved base excision repair (BER), a pathway that protects genome from consequences of oxidative damage. In this study we tested hypothesis expression coding SNP (rs3136797) mammalian cells could induce cancerous phenotype. Expression both human mouse induced double-strand breaks, chromosomal aberrations, transformation. Following treatment with an alkylating agent, expressing accumulated BER intermediate substrates, including single-strand breaks. The rs3136797 encodes P242R variant Pol protein analysis showed had slower catalytic rate than WT, although binds similarly to WT. Our results suggest people who carry may be at increased risk for cancer susceptibility.