INACTIVATION OF DNA PROOFREADING OBVIATES THE NEED FOR SOS INDUCTION IN FRAMESHIFT MUTAGENESIS

Translesion synthesis at replication-blocking lesions requires the ind uction of proteins that are controlled by the SOS system in Escherichi a coli, Of the proteins identified so far, UmuD', UmuC, and RecA were shown to facilitate replication across UV-light-induced lesions, yiel ding both error-free and mutagenic translesion-synthesis products. Sim ilar to UV lesions, N-2-acetylaminofluorene (AAF), a chemical carcinog en that forms covalent adducts at the C8 position of guanine residues, is a strong replication-blocking lesion. Frameshift mutations are ind uced efficiently by AAF adducts when located within short repetitive s equences in a two-step mechanism; AAF adducts incorporate a cytosine a cross from the lesion and then form a primer-template misaligned inter mediate that, upon elongation, yields frameshift mutations, Recently, we have shown that although elongation from the nonslipped intermediat e depends on functional umuDC(+) gene products, elongation from the sl ipped intermediate is umuDC(+)-independent but requires another, as ye t biochemically uncharacterized, SOS function, We now show that in DNA Polymerase III-proofreading mutant strains (dnaQ49 and mutD5 strains) , elongation from the slipped intermediate is highly efficient in the absence of SOS induction-in contrast to elongation from the nonslipped intermediate, which still requires UmuDC functions.