DNA single-strand break repair and spinocerebellar ataxia with axonal neuropathy-1.
DNA single-strand breaks (SSBs) are the commonest DNA lesions arising spontaneously in cells, and if not repaired may block transcription or may be converted into potentially lethal/clastogenic DNA double-strand breaks (DSBs). Recently, evidence has emerged that defects in the rapid repair of SSBs preferentially impact the nervous system. In particular, spinocerebellar ataxia with axonal neuropathy (SCAN1) is a human disease that is associated with mutation of TDP1 (tyrosyl DNA phosphodiesterase 1) protein and with a defect in repairing certain types of SSBs. Although SCAN1 is a rare neurodegenerative disorder, understanding the molecular basis of this disease will lead to better understanding of neurodegenerative processes. Here we review recent progress in our understanding of TDP1, single-strand break repair (SSBR), and neurodegenerative disease.
el-Khamisy
S F
SF
Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK.
Caldecott
K W
KW
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D004247:DNA / Q000235:genetics; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
D004247:DNA; D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human