We examined the inhibitory effect of chlorpromazine, a phenothiazine d
erivative, on SV40 DNA replication in a HeLa cell extract. The inhibit
ion by chlorpromazine was reversed by cardiolipin, phosphatidylinosito
l, phosphatidylglycerol, and phosphatidylserine. Studies on a staged r
eaction showed that the pre-elongation step was sensitive to chlorprom
azine: chlorpromazine-resistant DNA synthesis was observed when the dr
ug was added after the pre-elongation step. Analysis of replication pr
oducts by agarose gel electrophoresis revealed that some steps of DNA
chain elongation and maturation of closed circular forms were also sen
sitive to this drug.