Base excision repair in mitochondria, mitochondrial DNA copy number and telomere length and link to colorectal cancer outcome
Abstract
The dysfunction of mitochondria is one of the cancer hallmarks. Mitochondria evince a limited DNA repair capacity and compensate for damage by increasing the mitochondrial DNA copy number (mtDNA-CN). Current studies on the mtDNA-CN in cancer have, however, reported ambiguous results. In this context, base excision repair (BER) is the major repair pathway for oxidative DNA damage removal, taking place in nuclei and mitochondria. Both in nuclear and mitochondrial DNA (mtDNA), the repair process is initiated by DNA glycosylases, such as 8-oxoguanine DNA glycosylase 1 (OGG1), that recognize and incise N-glycosidic bonds between the damaged base and deoxyribose. MtDNA is exposed to reactive oxygen species more than nuclear DNA, in particular, due to its proximity to the electron transport chain. Functional
BER, keeping mtDNA intact, is necessary for the proper cell energetic metabolism and for preventing mtDNA mutations leading to carcinogenesis.