INHIBITION OF DNA UNWINDING AND ATPASE ACTIVITIES OF HUMAN DNA HELICASE-II BY CHEMOTHERAPEUTIC-AGENTS

DNA helicases catalyze the unwinding of duplex DNA and thus play impor tant roles in the processing of DNA, little is known about the effects of various cytotoxic or antitumor chemotherapeutic agents on purified human DNA helicases. We have determined the effect of actinomycin C-1 , VP-16, camptothecin, ethidium bromide, ellipticine, nogalamycin, nov obiocin, genistein, m-AMSA, aphidicolin and daunorubicin on the enzyma tic activities of purified human DNA helicase II which was identified as Ku autoantigen. Ku contains DNA helicase, ATPase and DNA end bindin g activities. Our data have shown that out of several chemotherapeutic agents tested ethidium bromide, actinomycin C-1, daunorubicin and nog alamycin were inhibitors of DNA unwinding activity of human DNA helica se II with ID50 values of 8.44 mu M, 11.68 mu M, 6.23 mu M and 0.42 mu M respectively. These inhibitors also inhibited the ATPase activity b ut not the DNA binding activity of this helicase. This inhibition coul d be due to binding of these drugs to DNA, thereby impeding the moveme nt of the helicase for unwinding action which may be their most import ant pharmacological function against cancer cells. (C) 1997 Academic P ress.