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

Abstract

Both in yeast and humans, DNA polymerase (Pol) (eta) functions in the error-free replication of UV-damaged DNA, and Pol(eta) 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 Pol(kappa) belongs to the same protein family as Pol(eta), Pol(kappa) shows no ability to bypass this DNA lesion and its biological function has remained unclear. Here, we examine Pol(kappa) for its ability to extend from primer-terminal mispairs opposite nondamaged and damaged DNA templates. We find that Pol(kappa) 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 Pol(kappa) in the extension of mismatched base pairs during normal DNA replication, and in addition, they implicate Pol(kappa) in the mutagenic bypass of T-T dimers. In its proficient mismatch extension ability, Pol(kappa) is more similar to the unrelated DNA polymerase zeta than it is to the phylogenetically related Pol(eta) or Pol(iota). Thus, in humans, Pol(kappa) would compete with Pol(zeta) for the extension of mismatched base pairs on damaged and undamaged DNAs.