E. coli DNA Pol II and eukaryotic Rev3 are B-family polymerases that can extend
primers past a damaged or mismatched site when the high-fidelity replicative
polymerases in the same family are ineffective. We report here the biochemical
and structural properties of DNA Pol II that facilitate this translesion
synthesis. DNA Pol II can extend primers past lesions either directly or by
template skipping, in which small protein cavities outside of the active site
accommodate looped-out template nucleotides 1 or 2 bp upstream. Because of
multiple looping-out alternatives, mutation spectra of bypass synthesis are
complicated. Moreover, translesion synthesis is enhanced by altered partitioning
of DNA substrate between the polymerase active site and the proofreading
exonuclease site. Compared to the replicative B family polymerases, DNA Pol II
has subtle amino acid changes remote from the active site that allow it to
replicate normal DNA with high efficiency yet conduct translesion synthesis when
needed.
