title: Repair of persistent strand breaks in the mitochondrial genome.
abstract: Oxidative DNA damage has been attributed to increased cancer incidence and premature aging phenotypes. Reactive oxygen species (ROS) are unavoidable byproducts of oxidative phosphorylation and are the major contributors of endogenous oxidative damage. To prevent the negative effects of ROS, cells have developed DNA repair mechanisms designed to specifically combat endogenous DNA modifications. The base excision repair (BER) pathway is primarily responsible for the repair of small non-helix distorting lesions and DNA single strand breaks. This repair pathway is found in all organisms, and in mammalian cells, consists of three related sub-pathways: short patch (SP-BER), long patch (LP-BER) and single strand break repair (SSBR). While much is known about nuclear BER, comparatively little is known about this pathway in the mitochondria, particularly the LP-BER and SSBR sub-pathways. There are a number of proteins that have recently been found to be involved in mitochondrial BER, including Cockayne syndrome proteins A and B (CSA and CSB), aprataxin (APTX), tryosyl-DNA phosphodiesterase 1 (TDP1), flap endonuclease 1 (FEN-1) and exonuclease G (EXOG). These significant advances in mitochondrial DNA repair may open new avenues in the management and treatment of a number of neurological disorders associated with mitochondrial dysfunction, and will be reviewed in further detail herein.
authors.affiliation: NIH Biomedical Research Center, 251 Bayview Boulevard, Baltimore, MD 21224, USA. sykorap@mail.nih.gov
authors.forename: Peter
authors.initials: P
authors.lastname: Sykora
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D045643:DNA Repair Enzymes