Cellular Deficiency of Werner Syndrome Protein or RECQ1 Promotes Genotoxic Potential of Hydroquinone and Benzo[a]pyrene Exposure.

[werner syndrome]

The 5 known RecQ helicases in humans (RECQ 1 , BLM , WRN , RECQL 4 , and RECQ 5 ) 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 RECQ 1 (the most abundant homolog of WRN ) in hydroquinone (HQ )- and benzo [a ]pyrene (BaP )-induced genotoxicity . Silencing of WRN or RECQ 1 expression in HeLa cells increased their sensitivity to HQ and BaP but elicited distinct DNA damage response . The RECQ 1 -depleted cells exhibited increased replication protein A phosphorylation , Chk 1 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 RECQ 1 -depleted cells were dependent on DNA-dependent protein kinase activity . Notably , loss of WRN in RECQ 1 -depleted cells ameliorated BaP toxicity . Collectively , our results provide first indication of nonredundant participation of WRN and RECQ 1 in protection from the potentially carcinogenic effects of BaP and HQ .