Overexpression of DNA glycosylase enhances the radiosensitivity in HeLa cells

Abstract

Ionizing radiation produces a unique form of DNA damage called clustered damage, which contains two or more lesions induced within the one or two helical turns of DNA. Clustered damage would be less readily repaired than isolated lesions. Therefore clustered damage might be biologically significant. In this report we showed that HeLaS3 cells transfected by hOGG1 type1a or type2a plasmid were more sensitive to gamma-rays than HeLaS3 cells without plasmid. Clustered damage produced by ionizing radiation might be converted to lethal double-strand breaks during attempted base excision repair. hOGG1 type1a protein localized in nuclei and hOGG1 type2a in mitochondria. The present results that overexpression of hOGG1 type2a protein enhanced the sensitivity to gamma-rays suggest that double-strand breaks are also induced by abortive base excision repair in mitochondrial genome. We are currently investigating the biological effects of clustered damages in human cells.