Translesion synthesis by TLS DNA polymerases. When the high-fidelity E. coli replicase, Pol III (yellow), encounters a leading-strand lesion (red X), it stalls, and a TLS polymerase (TLS Pol, gray) takes over the β sliding clamp (purple) to extend the leading strand across the lesion. After lesion bypass, Pol III resumes its function with the β clamp. The structure of a TLS DNA polymerase is shown (bottom), the archaeal Dbo4 (white) binding to DNA that contains a benzo[a]pyrene adduct (yellow).