Large deletions and untargeted substitutions induced by abasic site analog on leading versus lagging strand templates in human cells

The tetrahydrofuran-type abasic site analog (THF) induces large deletion mutations in human cells. To compare the large deletions induced by THF on leading and lagging strand templates, plasmid DNAs bearing the analog at a specific position outside the supF gene were introduced into human U2OS cells. The replicated DNAs recovered from the transfected cells were electroporated into an Escherichia coli indicator strain. THF on the lagging strand template produced more supF mutants than THF on the leading strand template. This unequal mutagenicity was due to the higher frequencies of not only large deletions but also untargeted base substitutions induced in the gene. These results suggested that both types of mutations occur more frequently when abasic sites are formed on the lagging strand template.