DNA polymerases II and V mediate respectively mutagenic (-2 frameshift) and error-free bypass of a single N-2-acetylaminofluorene adduct

The NarI sequence represents a strong mutation hot spot for -2 frameshift m utations induced by N-2-acetylaminofluorene (AAF), a strong chemical carcin ogen. Only when bound to the third (underlined) guanine (5 ' -GGC (G) under bar CC --> GGCC) can AAF trigger frameshift mutations, suggesting the invo lvement of a slipped replication intermediate with a two-nucleotide bulge. While base substitutions induced by UV light or abasic sites require DNA po lymerase V (Pol V; umuDC), the AAF-induced -2 frameshift pathway requires D NA polymerase II, the polB gene product. Interestingly, error-free bypass o f the G-AAF adduct requires Pol V. The genes encoding both Pol II and Pol V are induced by the SOS regulon, a co-ordinated cellular response to enviro nmental stress. A given lesion, G-AAF, can thus be bypassed by two SOS-cont rolled DNA polymerases (II and V), generating mutagenic(-2 frameshifts) and error-free replication products respectively. Therefore both Pol II and Po l V can compete for the blocked replication intermediate in the vicinity of the lesion and engage in replication by transiently replacing the replicat ive DNA Pol III. Our data suggest that, in order to cope with the large div ersity of existing DNA lesions, cells use a single or a combination of tran slesional DNA polymerases to achieve translesion synthesis.