Competitive inhibition of nicking--closing enzymes may explain some biological effects of DNA intercalators

Abstract

Intercalating agents cause varied and multiple biological effects. These include the inhibition of RNA and DNA synthesis, frameshift mutations and protein-associated DNA breaks. However, some non-intercalating analogs of intercalating compounds behave similarly. The model of DNA intercalation does not adequately explain all these biological effects. It is suggested here that intercalators and similar compounds may competitively inhibit the closing reaction of some nicking--closing enzymes. Hypothetical mechanisms built on this suggestion are presented for the formation of protein associated DNA breaks, frameshift mutation, inhibition of macromolecular synthesis, and recombination.