Base excision repair and the central nervous system

• Published in: Neuroscience Vol. 145; no. 4; pp. 1187 - 1200
• Main Authors: Wilson, D.M, McNeill, D.R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 14.04.2007
• Subjects: Animals; brain; Cell Survival - genetics; Central Nervous System - enzymology; Central Nervous System - physiopathology; DNA Damage - genetics; DNA repair; DNA Repair - genetics; DNA Repair Enzymes - genetics; Humans; Mitochondria - enzymology; Mitochondria - genetics; neurodegeneration; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - physiopathology; Neurology; Neurons - enzymology; Neurons - ultrastructure; oxidative damage; Oxidative Stress - genetics; POLβ; AP endonuclease 1; OGG1; neurodegeneration; ALS; NTH1; peripheral nervous system; amyotrophic lateral sclerosis; oculomotor apraxia type 1; tyrosyl-DNA phosphodiesterase; PNS; days post-coitum; SSBR; UDG; 5′-deoxyribose phosphate; MYH; CAA; AD; dRP; 7,8-dihydro-8-oxoguanine DNA glycosylase; Alzheimer’s disease; MutY DNA glycosylase homologue; base excision repair; MAG; single-strand break repair; chloroacetaldehyde; ROS; 7,8-dihydro-8-oxoguanine; NEIL1; endonuclease III homologue 1 glycosylase; oxidative damage; d.p.c; DNA repair; endonuclease VIII-like DNA glycosylase; TDG; reactive oxygen species; LIG1 or LIG3; 3-methyladenine DNA glycosylase; APE1; SCAN1; LIGASE 1/3; XRCC1; brain; X-ray cross-complementing 1; 8-oxo-dG; BER; PD; TDP1; polymerase β; thymidine DNA glycosylase; uracil DNA glycosylase; Parkinson’s disease
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2006.07.011

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 β, X-ray cross-complementing 1, and the DNA ligases.