Fidelity and Processivity of DNA Synthesis by DNA Polymerase κ, the Product of the Human DINB1 Gene

• Published in: The Journal of biological chemistry 2000-12, Vol.275 (50), p.39678
• Main Authors: Eiji Ohashi, Katarzyna Bebenek, Toshiro Matsuda, William J. Feaver, Valerie L. Gerlach, Errol C. Friedberg, Haruo Ohmori, Thomas A. Kunkel
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M005309200

Mammalian DNA polymerase κ (pol κ), a member of the UmuC/DinB nucleotidyl transferase superfamily, has been implicated in spontaneous mutagenesis. Here we show that human pol κ 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 κ 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 κ 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 κ is novel in comparison to any previously studied DNA polymerase, and is consistent with a role in spontaneous mutagenesis.