title: Base excision repair and the central nervous system.
abstract: Reactive oxygen species generated during normal cellular metabolism react with lipids, proteins, and nucleic acid. Evidence indicates that the accumulation of oxidative damage results in cellular dysfunction or deterioration. In particular, oxidative DNA damage can induce mutagenic replicative outcomes, leading to altered cellular function and/or cellular transformation. Additionally, oxidative DNA modifications can block essential biological processes, namely replication and transcription, triggering cell death responses. The major pathway responsible for removing oxidative DNA damage and restoring the integrity of the genome is base excision repair (BER). We highlight herein what is known about BER protein function(s) in the CNS, which in cooperation with the peripheral nervous system operates to control physical responses, motor coordination, and brain operation. Moreover, we describe evidence indicating that defective BER processing can promote post-mitotic (i.e. non-dividing) neuronal cell death and neurodegenerative disease. The focus of the review is on the core mammalian BER participants, i.e. the DNA glycosylases, AP endonuclease 1, DNA polymerase beta, X-ray cross-complementing 1, and the DNA ligases.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. wilsonda@grc.nia.nih.gov
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: D R
authors.initials: DR
authors.lastname: McNeill
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002490:Central Nervous System / Q000201:enzymology* / Q000503:physiopathology; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000201:enzymology / Q000648:ultrastructure; D018384:Oxidative Stress / Q000235:genetics*
chemical_list: D045643:DNA Repair Enzymes