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Originally published In Press as doi:10.1074/jbc.M009049200 on October 27, 2000

J. Biol. Chem., Vol. 276, Issue 3, 2263-2266, January 19, 2001
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Mismatch Extension Ability of Yeast and Human DNA Polymerase eta *

M. Todd Washington, Robert E. Johnson, Satya Prakash, and Louise PrakashDagger

From the Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061

DNA polymerase eta  (Poleta ) functions in error-free replication of UV-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 Poleta 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 Poleta in error-free translesion DNA synthesis, here we examine the ability of Poleta to extend from base mismatches. We find that both yeast and human Poleta extend from mismatched base pairs with a frequency of ~10-3 relative to matched base pairs. In the absence of efficient extension of mismatched primer termini, the ensuing dissociation of Poleta from DNA may favor the excision of mismatched nucleotides by a proofreading exonuclease. Thus, we expect DNA synthesis by Poleta to be more accurate than that predicted from the fidelity of nucleotide incorporation alone.

* This work was supported by National Institutes of Health Grant GM19261.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Sealy Center for Molecular Science, University of Texas Medical Branch, 6.104 Medical Research Bldg., 11th and Mechanic Sts., Galveston, TX 77555-1061. Tel.: 409-747-8601; Fax: 409-747-8608; E-mail: lprakash@scms.utmb.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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