Defective DNA repair and neurodegenerative disease.
Defects in cellular DNA repair processes have been linked to genome instability, heritable cancers, and premature aging syndromes. Yet defects in some repair processes manifest themselves primarily in neuronal tissues. This review focuses on studies defining the molecular defects associated with several human neurological disorders, particularly ataxia with oculomotor apraxia 1 (AOA1) and spinocerebellar ataxia with axonal neuropathy 1 (SCAN1). A picture is emerging to suggest that brain cells, due to their nonproliferative nature, may be particularly prone to the progressive accumulation of unrepaired DNA lesions.
Rass
Ulrich
U
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
Ahel
Ivan
I
West
Stephen C
SC
D000818:Animals; D001072:Apraxias / Q000235:genetics / Q000378:metabolism; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015840:Oculomotor Nerve Diseases / Q000235:genetics / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
C438188:APTX protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human; D045643:DNA Repair Enzymes