AI Article Synopsis
- DNA helicases are essential for unwinding DNA, and the study investigates the impact of various chemotherapy drugs on purified human DNA helicase II (Ku autoantigen).
- The agents tested include actinomycin C1, VP-16, and others, with ethidium bromide, actinomycin C1, daunorubicin, and nogalamycin identified as significant inhibitors of helicase activity.
- The inhibition likely occurs as these drugs bind to DNA, hindering the helicase's ability to unwind it, which may contribute to their effectiveness in treating cancer.
Article Abstract
DNA helicases catalyze the unwinding of duplex DNA and thus play important 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 C1, VP-16, camptothecin, ethidium bromide, ellipticine, nogalamycin, novobiocin, genistein, m-AMSA, aphidicolin and daunorubicin on the enzymatic activities of purified human DNA helicase II which was identified as Ku autoantigen. Ku contains DNA helicase, ATPase and DNA end binding activities. Our data have shown that out of several chemotherapeutic agents tested ethidium bromide, actinomycin C1, daunorubicin and nogalamycin were inhibitors of DNA unwinding activity of human DNA helicase II with ID50 values of 8.44 microM, 11.68 microM, 6.23 microM and 0.42 microM respectively. These inhibitors also inhibited the ATPase activity but not the DNA binding activity of this helicase. This inhibition could be due to binding of these drugs to DNA, thereby impeding the movement of the helicase for unwinding action which may be their most important pharmacological function against cancer cells.
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| http://dx.doi.org/10.1006/bbrc.1997.7021 | DOI Listing |
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