Mismatch extension ability of yeast and human DNA polymerase η

DNA polymerase eta (Pol eta) functions in error-free replication of W-damaged DNA, and in vitro it efficiently bypasses a cis-syn T-T dimer by incorporating two adenines opposite the lesion. Steady state kinetic studies have shown that both yeast and human Pol eta are low-fidelity enzymes, and they misincorporate nucleotides with a frequency of 10(-2)-10(-3) on both undamaged and T-T dimer-containing DNA templates. To better understand the role of Pol eta in error-free translesion DNA synthesis, here we examine the ability of Pol eta to extend from base mismatches. We find that both yeast and human Pol eta extend from mismatched base pairs with a frequency of similar to 10(-3) relative to matched base pairs. In the absence of efficient extension of mismatched primer termini, the ensuing dissociation of Pol eta from DNA may favor the excision of mismatched nucleotides by a proofreading exonuclease. Thus, we expect DNA synthesis by Pol eta to be more accurate than that predicted from the fidelity of nucleotide incorporation alone.