title: Risky repair: DNA-protein crosslinks formed by mitochondrial base excision DNA repair enzymes acting on free radical lesions.
abstract: Oxygen is both necessary and dangerous for aerobic cell function. ATP is most efficiently made by the electron transport chain, which requires oxygen as an electron acceptor. However, the presence of oxygen, and to some extent the respiratory chain itself, poses a danger to cellular components. Mitochondria, the sites of oxidative phosphorylation, have defense and repair pathways to cope with oxidative damage. For mitochondrial DNA, an essential pathway is base excision repair, which acts on a variety of small lesions. There are instances, however, in which attempted DNA repair results in more damage, such as the formation of a DNA-protein crosslink trapping the repair enzyme on the DNA. That is the case for mitochondrial DNA polymerase γ acting on abasic sites oxidized at the 1-carbon of 2-deoxyribose. Such DNA-protein crosslinks presumably must be removed in order to restore function. In nuclear DNA, ubiquitylation of the crosslinked protein and digestion by the proteasome are essential first processing steps. How and whether such mechanisms operate on DNA-protein crosslinks in mitochondria remains to be seen.
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA.
authors.forename: Rachel Audrey
authors.initials: RA
authors.lastname: Caston
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA. Electronic address: bruce.demple@stonybrook.edu.
authors.forename: Bruce
authors.initials: B
authors.lastname: Demple
mesh_terms: D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D000074002:DNA Polymerase gamma / Q000378:metabolism*; D004260:DNA Repair; D003855:Deoxyribose / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018736:DNA Adducts; D005609:Free Radicals; D003855:Deoxyribose; D000074002:DNA Polymerase gamma; D046988:Proteasome Endopeptidase Complex
keywords: 2-deoxyribonolactone; AP lyase; DNA polymerase beta; DNA polymerase gamma; Oxidized abasic sites