Transcriptional Footprinting of DrugDNA Interactions

There are now approx 50 registered anticancer drugs that are in routine clinical use as chemotherapeutic agents (1 –3 ). Of these, over half are known to interact with DNA, either by intercalation (e.g., doxorubicin, mitoxantrone), groove binding (e.g., distamycin), formation of adducts or crosslinks (e.g., melphalan, cisplatin, mitomycin C), or by incorporation of modified bases (e.g., 5-fluorouracil, 6-thioguanine). There has therefore been a great effort over many years to establish where on the DNA these drugs interact, with the expectation that a good understanding of the nature of the DNA receptor site would lead to the design of a new generation of these drugs.