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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
Mismatch Extension Ability of Yeast and Human DNA Polymerase
*
M. Todd
Washington,
Robert E.
Johnson,
Satya
Prakash, and
Louise
Prakash
From the Sealy Center for Molecular Science, University of Texas
Medical Branch, Galveston, Texas 77555-1061
DNA polymerase (Pol ) 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 Pol 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 in error-free translesion DNA synthesis, here we
examine the ability of Pol to extend from base mismatches. We find
that both yeast and human Pol 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 Pol from DNA may favor the
excision of mismatched nucleotides by a proofreading exonuclease. Thus,
we expect DNA synthesis by Pol 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.
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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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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