Mismatch extension ability of yeast and human DNA polymerase eta

DNA polymerase eta (Pol eta) functions in error-free replication of W-damag ed DNA, and in vitro it efficiently bypasses a cis-syn T-T dimer by incorpo rating 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 undama ged and T-T dimer-containing DNA templates. To better understand the role o f Pol eta in error-free translesion DNA synthesis, here we examine the abil ity 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 exte nsion of mismatched primer termini, the ensuing dissociation of Pol eta fro m DNA may favor the excision of mismatched nucleotides by a proofreading ex onuclease. Thus, we expect DNA synthesis by Pol eta to be more accurate tha n that predicted from the fidelity of nucleotide incorporation alone.