Human DNA polymerase κ synthesizes DNA with extraordinarily low fidelity

Yanbin Zhang, Fenghua Yuan, Hua Xin, Xiaohua Wu, Deepak K. Rajpal, Danzhou Yang, Zhigang Wang

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Escherichia coli DNA polymerase IV encoded by the dinB gene is involved in untargeted mutagenesis. Its human homologue is DNA polymerase κ (Polκ) encoded by the DINB1 gene. Our recent studies have indicated that human Polκ is capable of both error-free and error-prone translesion DNA synthesis in vitro. However, it is not known whether human Polκ also plays a role in untargeted mutagenesis. To examine this possibility, we have measured the fidelity of human Polκ during DNA synthesis from undamaged templates. Using kinetic measurements of nucleotide incorporations and a fidelity assay with gapped M13mp2 DNA, we show that human Polκ synthesizes DNA with extraordinarily low fidelity. At the lacZα target gene, human Polκ made on average one error for every 200 nucleotides synthesized, with a predominant T→G transversion mutation at a rate of 1/147. The overall error rate of human Polκ is 1.7-fold lower than human Polκ, but 33-fold higher than human Polβ, a DNA polymerase with very low fidelity. Thus, human Polκ is one of the most inaccurate DNA polymerases known. These results support a role for human Polκ in untargeted mutagenesis surrounding a DNA lesion and in DNA regions without damage.

Original languageEnglish (US)
Pages (from-to)4147-4156
Number of pages10
JournalNucleic acids research
Volume28
Issue number21
StatePublished - Nov 1 2000

ASJC Scopus subject areas

  • Genetics

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    Zhang, Y., Yuan, F., Xin, H., Wu, X., Rajpal, D. K., Yang, D., & Wang, Z. (2000). Human DNA polymerase κ synthesizes DNA with extraordinarily low fidelity. Nucleic acids research, 28(21), 4147-4156.