title: Brain capacity for repair of oxidatively damaged DNA and preservation of neuronal function.
abstract: Accumulation of oxidative DNA damage in the human brain has been implicated in etiologies of post-traumatic and age-associated declines in neuronal function. In neurons, because of high metabolic rates and prolonged life span, exposure to free radicals is intense and risk for accumulation of damaged DNA is amplified. While data indicate that the brain is equipped to repair nuclear and mitochondrial DNA, it is unclear whether repair is executed by distinct subsets of the DNA-repair machinery. Likewise, there are no firm assessments of brain capacity for accurate DNA repair under normal and more so compromised conditions. Consequently, the scope of DNA repair in the brain and the impact of resolution of oxidative lesions on neuronal survival and function remain largely unknown. This review considers evidences for brain levels and activities of the base excision repair (BER) pathway in the context of newly available, comprehensive in situ hybridization analyses of genes encoding repair enzymes. These analyses suggest that not all subsets of BER are equally represented in the brain. Because BER is the major repair process for oxidatively damaged DNA, to what extent parsimonious BER may contribute to development of neuronal dysfunction and brain injury under compromised conditions, is discussed.
authors: Department of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1220, USA. elenglan@utmb.edu
authors: Ella W
authors: EW
authors: Englander
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D001930:Brain Injuries / Q000209:etiology / Q000503:physiopathology; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000201:enzymology* / Q000502:physiology; D018384:Oxidative Stress; D051381:Rats
chemical_list: D045643:DNA Repair Enzymes