title: Base Excision Repair in the Mitochondria.
abstract: The 16.5 kb human mitochondrial genome encodes for 13 polypeptides, 22 tRNAs and 2 rRNAs involved in oxidative phosphorylation. Mitochondrial DNA (mtDNA), unlike its nuclear counterpart, is not packaged into nucleosomes and is more prone to the adverse effects of reactive oxygen species (ROS) generated during oxidative phosphorylation. The past few decades have witnessed an increase in the number of proteins observed to translocate to the mitochondria for the purposes of mitochondrial genome maintenance. The mtDNA damage produced by ROS, if not properly repaired, leads to instability and can ultimately manifest in mitochondrial dysfunction and disease. The base excision repair (BER) pathway is employed for the removal and consequently the repair of deaminated, oxidized, and alkylated DNA bases. Specialized enzymes called DNA glycosylases, which locate and cleave the damaged base, catalyze the first step of this highly coordinated repair pathway. This review focuses on members of the four human BER DNA glycosylase superfamilies and their subcellular localization in the mitochondria and/or the nucleus, as well as summarizes their structural features, biochemical properties, and functional role in the excision of damaged bases.
authors.affiliation: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, Vermont.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Prakash
authors.affiliation: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, Vermont.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Doublié
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D045647:DNA Glycosylases / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010085:Oxidative Phosphorylation
chemical_list: D004272:DNA, Mitochondrial; D045647:DNA Glycosylases
keywords: BASE EXCISION REPAIR; DNA GLYCOSYLASES; MITOCHONDRIAL DNA DAMAGE AND RESPONSE; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE PHOSPHORYLATION; REACTIVE OXYGEN SPECIES