Mutagenic DNA repair in Streptomyces.

Abstract

S. fradiae JS6 (mcr-6) is defective in the repair of potentially lethal damage to DNA induced by mitomycin C (MC), hydroxylamine (NH2OH), methyl methanesulfonate (MMS), 4-nitroquinoline-1-oxide (NQO), N-methyl-N''-nitro-N-nitrosoguanidine (MNNG) and UV light, but it exhibits nearly normal sensitivity to ethyl methanesulfonate (EMS)-induced lethality. JS6 is substantially less mutable by MNNG, MMS, NQO, UV, NH2OH and also EMS than is the parental strain. A spontaneous revertant of JS6 showed wild-type levels of resistance to all of these agents and wild-type levels of induced mutagenesis, indicating that a single mutation caused the multiple traits displayed by JS6. The mcr-6 gene product thus appears to control an error prone (mutagenic) DNA repair system. Mediation of EMS mutagenesis by an error-prone repair pathway in S. fradiae, rather than by direct mispairing as in Escherichia coli, suggests that the streptomycetes have evolved more efficient error avoidance mechanisms than those commonly observed in the single-celled eubacteria.