Studies on the inhibition of repair of ultraviolet- and methyl methanesulfonate-induced damage in the DNA of human fibroblasts by novobiocin.

Abstract

The antibiotic novobiocin is shown to alter the sedimentation properties of human cellular DNA in alkaline sucrose. This alteration is at least partially due to increased DNA-protein binding in the cell in the presence of novobiocin. Pyrimidine dimer analysis and repair replication studies support previous reports that novobiocin inhibits repair of UV damage in human cells but we find this block to be shortlived. It is also shown that novobiocin is ineffective at blocking "long-patch" repair induced by methyl methanesulfonate as measured both by CsCl density centrifugation and the ara-C inhibition technique. However, the accumulation of breaks in MMS-treated cellular DNA in the presence of novobiocin suggests that some "short-patch" alkylation repair may be inhibited by the antibiotic. These findings are discussed in light of the proposal that novobiocin may inhibit a DNA gyrase-like activity in human as in bacterial cells.