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Originally published In Press as doi:10.1074/jbc.M005309200 on September 26, 2000

J. Biol. Chem., Vol. 275, Issue 50, 39678-39684, December 15, 2000
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Fidelity and Processivity of DNA Synthesis by DNA Polymerase kappa , the Product of the Human DINB1 Gene*

Eiji OhashiDagger §, Katarzyna Bebenek§, Toshiro Matsuda§, William J. Feaver||, Valerie L. Gerlach||**, Errol C. Friedberg||, Haruo OhmoriDagger , and Thomas A. KunkelDagger Dagger §§

From the Dagger  Institute for Virus Research, Kyoto University, Sakyo, Kyoto 606-8507, Japan, the || Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9072, and the  Laboratory of Molecular Genetics and Dagger Dagger  Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Mammalian DNA polymerase kappa  (pol kappa ), a member of the UmuC/DinB nucleotidyl transferase superfamily, has been implicated in spontaneous mutagenesis. Here we show that human pol kappa  copies undamaged DNA with average single-base substitution and deletion error rates of 7 × 10-3 and 2 × 10-3, respectively. These error rates are high when compared to those of most other DNA polymerases. pol kappa  also has unusual error specificity, producing a high proportion of T·CMP mispairs and deleting and adding non-reiterated nucleotides at extraordinary rates. Unlike other members of the UmuC/DinB family, pol kappa  can processively synthesize chains of 25 or more nucleotides. This moderate processivity may reflect a contribution of C-terminal residues, which include two zinc clusters. The very low fidelity and moderate processivity of pol kappa  is novel in comparison to any previously studied DNA polymerase, and is consistent with a role in spontaneous mutagenesis.

* This study was supported in part by National Cancer Institute Grant CA-69029 (to E. C. F.).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.

§ These authors contributed equally to this study.

** Supported by Postdoctoral Fellowship CA-75733 from the National Cancer Institute.

§§ To whom correspondence should be addressed: Laboratory of Structural Biology, National Institute of Environmental Health Sciences, 111 T. W. Alexander Dr., P. O. Box 12233, Research Triangle Park, NC 27709. Tel.: 919-541-2644, Fax: 919-541-7613; E-mail: kunkel@niehs.nih.gov.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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