Human DINB1-encoded DNA polymerase κ is a promiscuous extender of mispaired primer termini

Both in yeast and humans, DNA polymerase (Pol) η functions in the error-free replication of UV-damaged DNA, and Polη has the unique ability to efficiently replicate through a cis-syn thymine-thymine (T-T) dimer by inserting two As opposite the two Ts of the dimer. Although human DINB1-encoded Polκ belongs to the same protein family as Polη, Polκ shows no ability to bypass this DNA lesion and its biological function has remained unclear. Here, we examine Polκ for its ability to extend from primer-terminal mispairs opposite nondamaged and damaged DNA templates. We find that Polκ is a promiscuous extender of primer-terminal mispairs opposite nondamaged DNA templates, and interestingly, it is also very efficient at extending from a G opposite the 3′T of a T-T dimer. These observations provide biochemical evidence for a role of Polκ in the extension of mismatched base pairs during normal DNA replication, and in addition, they implicate Polκ in the mutagenic bypass of T-T dimers. In its proficient mismatch extension ability, Polκ is more similar to the unrelated DNA polymerase ζ than it is to the phylogenetically related Polη or Polι. Thus, in humans, Polκ would compete with Polζ for the extension of mismatched base pairs on damaged and undamaged DNAs.