Fidelity and processivity of DNA synthesis by DNA polymerase κ, the product of the human DINB1 gene

Eiji Ohashi, Katarzyna Bebenek, Toshiro Matsuda, William J. Feaver, Valerie L. Gerlach, Errol C. Friedberg, Haruo Ohmori, Thomas A. Kunkel

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)39678-39684
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number50
DOIs
Publication statusPublished - Dec 15 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ohashi, E., Bebenek, K., Matsuda, T., Feaver, W. J., Gerlach, V. L., Friedberg, E. C., Ohmori, H., & Kunkel, T. A. (2000). Fidelity and processivity of DNA synthesis by DNA polymerase κ, the product of the human DINB1 gene. Journal of Biological Chemistry, 275(50), 39678-39684. https://doi.org/10.1074/jbc.M005309200