title: Cellular deficiency of Werner syndrome protein or RECQ1 promotes genotoxic potential of hydroquinone and benzo[a]pyrene exposure.
abstract: The 5 known RecQ helicases in humans (RECQ1, BLM, WRN, RECQL4, and RECQ5) have demonstrated roles in diverse genome maintenance mechanisms but their functions in safeguarding the genome from environmental toxicants are poorly understood. Here, we have evaluated a potential role of WRN (mutated in Werner syndrome) and RECQ1 (the most abundant homolog of WRN) in hydroquinone (HQ)- and benzo[a]pyrene (BaP)-induced genotoxicity. Silencing of WRN or RECQ1 expression in HeLa cells increased their sensitivity to HQ and BaP but elicited distinct DNA damage response. The RECQ1-depleted cells exhibited increased replication protein A phosphorylation, Chk1 activation, and DNA double-strand breaks (DSBs) as compared to control or WRN-depleted cells following exposure to BaP treatment. The BaP-induced DSBs in RECQ1-depleted cells were dependent on DNA-dependent protein kinase activity. Notably, loss of WRN in RECQ1-depleted cells ameliorated BaP toxicity. Collectively, our results provide first indication of nonredundant participation of WRN and RECQ1 in protection from the potentially carcinogenic effects of BaP and HQ.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, NW, Washington, DC, USA.
authors.forename: Mamatha
authors.initials: M
authors.lastname: Garige
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, NW, Washington, DC, USA sudha.sharma@howard.edu.
authors.forename: Sudha
authors.initials: S
authors.lastname: Sharma
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D001564:Benzo(a)pyrene / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage; D005090:Exodeoxyribonucleases / Q000172:deficiency* / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D010766:Phosphorylation; D034622:RNA Interference; D053484:RecQ Helicases / Q000172:deficiency* / Q000235:genetics*; D000071657:Werner Syndrome Helicase
chemical_list: D006873:Hydroquinones; D009153:Mutagens; D001564:Benzo(a)pyrene; D064007:Ataxia Telangiectasia Mutated Proteins; D005090:Exodeoxyribonucleases; C506725:RECQL protein, human; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C031927:hydroquinone
keywords: DNA damage; DNA repair; RecQ; carcinogen; environmental; genomic instability; genotoxic; helicase; replication stress