Monofunctional alkylating agent-induced inactivation, mutagenesis and DNA degradation in an Escherichia coli mutant deficient in DNA polymerase.

Abstract

The DNA polymerase deficient mutantE. coli P3478polA1 is extremely sensitive to the lethal action of N-methyl-N′-nitro-N-nitrosoguanidine (NG) and methyl-methanesulfonate (MMS). ThepolA1 mutant has an almost unaffected mutability induced by NG or MMS and shows reduced ability to propagate MMS-treated phage T7. NG and MMS induce marked breakdown of DNA and inhibit significantly DNA synthesis in thepolA1 mutant. The obtained results suggest the thepolA1 mutant is unable to repair single-strand breaks of DNA induced by monofunctional alkylating agents. The suggestion is confirmed by the demonstrated sensitivity of thepolA1 mutant to thymine starvation (TS).