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Molecular and Cellular Biology, October 2000, p. 7099-7108, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Preferential Incorporation of G Opposite Template T by the Low-Fidelity Human DNA Polymerase iota

Yanbin Zhang, Fenghua Yuan, Xiaohua Wu, and Zhigang Wang*

Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536

Received 19 June 2000/Returned for modification 3 July 2000/Accepted 7 July 2000

DNA polymerase activity is essential for replication, recombination, repair, and mutagenesis. All DNA polymerases studied so far from any biological source synthesize DNA by the Watson-Crick base-pairing rule, incorporating A, G, C, and T opposite the templates T, C, G, and A, respectively. Non-Watson-Crick base pairs would lead to mutations. In this report, we describe the ninth human DNA polymerase, Poliota , encoded by the RAD30B gene. We show that human Poliota violates the Watson-Crick base-pairing rule opposite template T. During base selection, human Poliota preferred T-G base pairing, leading to G incorporation opposite template T. The resulting T-G base pair was less efficiently extended by human Poliota compared to the Watson-Crick base pairs. Consequently, DNA synthesis frequently aborted opposite template T, a property we designated the T stop. This T stop restricted human Poliota to a very short stretch of DNA synthesis. Furthermore, kinetic analyses show that human Poliota copies template C with extraordinarily low fidelity, misincorporating T, A, and C with unprecedented frequencies of 1/9, 1/10, and 1/11, respectively. Human Poliota incorporated one nucleotide opposite a template abasic site more efficiently than opposite a template T, suggesting a role for human Poliota in DNA lesion bypass. The unique features of preferential G incorporation opposite template T and T stop suggest that DNA Poliota may additionally play a specialized function in human biology.

* Corresponding author. Mailing address: 306 Health Sciences Research Bldg., Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536. Phone: (859) 323-5784. Fax: (859) 323-1059. E-mail: zwang{at}pop.uky.edu.

Molecular and Cellular Biology, October 2000, p. 7099-7108, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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