A MAJOR ROLE FOR BACTERIOPHAGE T4 DNA POLYMERASE IN FRAMESHIFT MUTAGENESIS

Lynn S. Ripley ¹ and Nadja B. Shoemaker ¹

¹ Laboratory of Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709

T4 DNA polymerase strongly influences the frequency and specificity of frameshift mutagenesis. Fifteen of 19 temperature-sensitive alleles of the DNA polymerase gene substantially influenced the reversion frequencies of frameshift mutations measured in the T4 rII genes. Most polymerase mutants increased frameshift frequencies, but a few alleles (previously noted as antimutators for base substitution mutations) decreased the frequencies of certain frameshifts while increasing the frequencies of others. The various patterns of enhanced or decreased frameshift mutation frequencies suggest that T4 DNA polymerase is likely to play a variety of roles in the metabolic events leading to frameshift mutation. A detailed genetic study of the specificity of the mutator properties of three DNA polymerase alleles (tsL56, tsL98 and tsL88) demonstrated that each produces a distinctive frameshift spectrum. Differences in frameshift frequencies at similar DNA sequences within the rII genes, the influence of mutant polymerase alleles on these frequencies, and the presence or absence of the dinucleotide sequence associated with initiation of Okazaki pieces at the frameshift site has led us to suggest that the discontinuities associated with discontinuous DNA replication may contribute to spontaneous frameshift mutation frequencies in T4.

This article has been cited by other articles:

				B. P. Muniappan and W. G. Thilly The DNA Polymerase {beta} Replication Error Spectrum in the Adenomatous Polyposis Coli Gene Contains Human Colon Tumor Mutational Hotspots Cancer Res., June 1, 2002; 62(11): 3271 - 3275. [Abstract] [Full Text] [PDF]

				M. I. Hadjimarcou, R. J. Kokoska, T. D. Petes, and L. J. Reha-Krantz Identification of a Mutant DNA Polymerase {{delta}} in Saccharomyces cerevisiae With an Antimutator Phenotype for Frameshift Mutations Genetics, May 1, 2001; 158(1): 177 - 186. [Abstract] [Full Text]

				M. F. Goodman and D. K. Fygenson DNA Polymerase Fidelity : From Genetics Toward a Biochemical Understanding Genetics, April 1, 1998; 148(4): 1475 - 1482. [Abstract] [Full Text] [PDF]

				R. M. Schaaper Antimutator Mutants in Bacteriophage T4 and Escherichia coli Genetics, April 1, 1998; 148(4): 1579 - 1585. [Abstract] [Full Text] [PDF]

				F. J. Wang and L. S. Ripley The Spectrum of Acridine Resistant Mutants of Bacteriophage T4 Reveals Cryptic Effects of the tsL141 DNA Polymerase Allele on Spontaneous Mutagenesis Genetics, April 1, 1998; 148(4): 1655 - 1665. [Abstract] [Full Text] [PDF]

				S. Rangarajan, G. Gudmundsson, Z. Qiu, P. L. Foster, and M. F. Goodman Escherichia coli DNA polymerase II catalyzes chromosomal and episomal DNA synthesis in vivo PNAS, February 4, 1997; 94(3): 946 - 951. [Abstract] [Full Text] [PDF]