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XRCC1 protects against the lethality of induced oxidative DNA damage in nondividing neural cells.


ABSTRACT: XRCC1 is a critical scaffold protein that orchestrates efficient single-strand break repair (SSBR). Recent data has found an association of XRCC1 with proteins causally linked to human spinocerebellar ataxias-aprataxin and tyrosyl-DNA phosphodiesterase 1-implicating SSBR in protection against neuronal cell loss and neurodegenerative disease. We demonstrate herein that shRNA lentiviral-mediated XRCC1 knockdown in human SH-SY5Y neuroblastoma cells results in a largely selective increase in sensitivity of the nondividing (i.e. terminally differentiated) cell population to the redox-cycling agents, menadione and paraquat; this reduced survival was accompanied by an accumulation of DNA strand breaks. Using hypoxanthine-xanthine oxidase as the oxidizing method, XRCC1 deficiency affected both div

SUBMITTER: Kulkarni A 

PROVIDER: S-EPMC2528184 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature