The processing of a Benzo(a)pyrene adduct into a frameshift or a base substitution mutation requires a different set of genes in Escherichia coli

Replication through a single DNA lesion may give rise to a panel of transle sion synthesis (TLS) events, which comprise error-free TLS, base substituti ons and frameshift mutations. In order to determine the genetic control of the various TLS events induced by a single lesion, we have chosen the major N2-dG adduct of (+)-anti-Benzo(a)pyrene diol epoxide [(+)-anti-BPDE] adduc t located within a short run of guanines as a model lesion. Within this seq uence context, in addition to the major event, i.e. error-free TLS, the add uct also induces base substitutions (mostly G --> T transversions) and -1 f rameshift mutations. The pathway leading to G --> T base substitution mutag enesis appears to be SOS independent, suggesting that TLS is most probably performed by the replicative Pol III holoenzyme itself. In contrast, both e rror-free and frameshift TLS pathways are dependent upon SOS-encoded functi ons that belong to the pool of inducible DNA polymerases specialized in TLS (translesional DNA polymerases), namely umuDC (Pol V) and dinB (Pol IV). I t is likely that, given the diversity of conformations that can be adopted by lesion-containing replication intermediates, cells use one or several tr anslesional DNA polymerases to achieve TLS.