title: Enzymology of mitochondrial base excision repair.
abstract: A number of laboratories have shown that those types of DNA damage that are generally reparable by base excision repair are efficiently repaired in mtDNA. In contrast, most types of damage that require other sorts of repair machinery are not effectively repaired in mtDNA. We have shown that a set of highly purified mitochondrial proteins, including AP endonuclease (APE), DNA polymerase gamma, and mtDNA ligase, is capable of efficiently repairing abasic (AP) sites in mtDNA. These three enzymes appear to conduct all four steps in a conventional BER mechanism: incision, removal of the 5'-deoxyribosephosphate by dRP lyase, polymerization, and ligation. Both DNA polymerase gamma and mtDNA ligase possess some dRP lyase activity. DNA polymerase gamma is a member of the family A of DNA polymerases, with clear homology to DNA pol I of E. coli, while mtDNA ligase is an alternatively expressed form of DNA ligase III. The dRP lyase activities discovered in these mitochondrial enzymes are not unique, but are found in all representatives tested of the family-A DNA polymerases and of the ATP-dependent DNA ligases. These dRP lyase activities have low turnover rates that may have important implications for the overall process of BER. All proteins involved in maintenance of mtDNA are encoded in the nuclear genome and must be directed to mitochondria in order to act on mtDNA. Thus, it is evident that the scope of DNA repair activities undertaken within mitochondria is determined by the set of nucleus-encoded DNA repair enzymes that are capable of being imported into the organelle. A review of DNA repair proteins that may be imported into mitochondria in various organisms will be presented.
authors.affiliation: Department of Pharmacological Sciences, SUNY at Stony Brook, Stony Brook, New York 11794, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Bogenhagen
authors.forename: K G
authors.initials: KG
authors.lastname: Pinz
authors.forename: R M
authors.initials: RM
authors.lastname: Perez-Jannotti
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D019757:Carbon-Oxygen Lyases / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics* / Q000378:metabolism; D000074002:DNA Polymerase gamma; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D043223:Deoxyribonuclease IV (Phage T4-Induced); D005656:Fungal Proteins / Q000235:genetics; D005796:Genes; D006801:Humans; D051379:Mice; D018384:Oxidative Stress; D000075223:Poly-ADP-Ribose Binding Proteins; D017386:Sequence Homology, Amino Acid; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004272:DNA, Mitochondrial; D005656:Fungal Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human; C000618818:Lig3 protein, mouse