Depletion of WRN enhances DNA damage in HeLa cells exposed to the benzene metabolite, hydroquinone

摘要: Werner syndrome is a progeroid disorder caused by mutations of the WRN gene. The encoded protein belongs to family RecQ helicases that plays role in maintenance genomic stability. Single nucleotide polymorphisms have been associated with an increased risk for some cancers and were recently linked benzene hematotoxicity. To further address toxicity, we employed RNA interference (RNAi) silence endogenous HeLa cells examined susceptibility these WRN-depleted toxic effects metabolite hydroquinone. used as experimental model because RNAi highly effective this system producing almost complete depletion target protein. Depletion led decrease cell proliferation enhanced hydroquinone cytotoxicity revealed increase necrosis. treated also displayed amount DNA double-strand breaks determined Comet assay, elevated damage response indicated sevenfold induction gammaH2AX acetyl-p53 (Lys373 Lys382) over control levels. Together, results show important protection against toxicity hydroquinone, specifically mounting normal following breaks. Further studies bone marrow-derived stem or progenitor are required confirm our findings expand ability extrapolate humans.