Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Jul;84(13):4450–4454. doi: 10.1073/pnas.84.13.4450

Next-nucleotide effects in mutations driven by DNA precursor pool imbalances at the aprt locus of Chinese hamster ovary cells.

G Phear, J Nalbantoglu, M Meuth
PMCID: PMC305107  PMID: 3474614

Abstract

Imbalances of the intracellular pools of the precursors of DNA synthesis, the deoxyribonucleoside triphosphates, produce marked shifts in the spectrum of mutations at the aprt locus of Chinese hamster ovary cells. Mutations induced by excess dTTP or dCTP are dominated by misincorporation of the nucleotide in excess, as determined by sequence analysis of cloned mutant genes. The shift in spectrum is also apparently influenced by the nucleotides surrounding the one altered--those 3' to the nucleotide misincorporated being present in excess in most of the mutant genes characterized. Since next-nucleotide effects are a property of DNA polymerases with "proofreading" activities, our data suggest that this function is part of the mammalian DNA replication complex.

Full text

PDF
4453

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bjursell G., Reichard P. Effects of thymidine on deoxyribonucleoside triphosphate pools and deoxyribonucleic acid synthesis in Chinese hamster ovary cells. J Biol Chem. 1973 Jun 10;248(11):3904–3909. [PubMed] [Google Scholar]
  3. Boersma D., McGill S. M., Mollenkamp J. W., Roufa D. J. Emetine resistance in Chinese hamster cells is linked genetically with an altered 40S ribosomal subunit protein, S20. Proc Natl Acad Sci U S A. 1979 Jan;76(1):415–419. doi: 10.1073/pnas.76.1.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradley M. O., Sharkey N. A. Mutagenicity of thymidine to cultured Chinese hamster cells. Nature. 1978 Aug 10;274(5671):607–608. doi: 10.1038/274607a0. [DOI] [PubMed] [Google Scholar]
  5. Bridges B. A., Law J., Munson R. J. Mutagenesis in Escherichia coli. II. Evidence for a common pathway for mutagenesis by ultraviolet light, ionizing radiation and thymine deprivation. Mol Gen Genet. 1968;103(3):266–273. doi: 10.1007/BF00273698. [DOI] [PubMed] [Google Scholar]
  6. Brutlag D., Kornberg A. Enzymatic synthesis of deoxyribonucleic acid. 36. A proofreading function for the 3' leads to 5' exonuclease activity in deoxyribonucleic acid polymerases. J Biol Chem. 1972 Jan 10;247(1):241–248. [PubMed] [Google Scholar]
  7. DePamphilis M. L., Wassarman P. M. Replication of eukaryotic chromosomes: a close-up of the replication fork. Annu Rev Biochem. 1980;49:627–666. doi: 10.1146/annurev.bi.49.070180.003211. [DOI] [PubMed] [Google Scholar]
  8. Degnen G. E., Cox E. C. Conditional mutator gene in Escherichia coli: isolation, mapping, and effector studies. J Bacteriol. 1974 Feb;117(2):477–487. doi: 10.1128/jb.117.2.477-487.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dohet C., Wagner R., Radman M. Repair of defined single base-pair mismatches in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Jan;82(2):503–505. doi: 10.1073/pnas.82.2.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eriksson S., Thelander L., Akerman M. Allosteric regulation of calf thymus ribonucleoside diphosphate reductase. Biochemistry. 1979 Jul 10;18(14):2948–2952. doi: 10.1021/bi00581a005. [DOI] [PubMed] [Google Scholar]
  11. Fersht A. R. Fidelity of replication of phage phi X174 DNA by DNA polymerase III holoenzyme: spontaneous mutation by misincorporation. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4946–4950. doi: 10.1073/pnas.76.10.4946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fersht A. R., Knill-Jones J. W. DNA polymerase accuracy and spontaneous mutation rates: frequencies of purine.purine, purine.pyrimidine, and pyrimidine.pyrimidine mismatches during DNA replication. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4251–4255. doi: 10.1073/pnas.78.7.4251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goncalves O., Drobetsky E., Meuth M. Structural alterations of the aprt locus induced by deoxyribonucleoside triphosphate pool imbalances in Chinese hamster ovary cells. Mol Cell Biol. 1984 Sep;4(9):1792–1799. doi: 10.1128/mcb.4.9.1792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hibner U., Alberts B. M. Fidelity of DNA replication catalysed in vitro on a natural DNA template by the T4 bacteriophage multi-enzyme complex. Nature. 1980 May 29;285(5763):300–305. doi: 10.1038/285300a0. [DOI] [PubMed] [Google Scholar]
  15. Karawya E., Swack J., Albert W., Fedorko J., Minna J. D., Wilson S. H. Identification of a higher molecular weight DNA polymerase alpha catalytic polypeptide in monkey cells by monoclonal antibody. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7777–7781. doi: 10.1073/pnas.81.24.7777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kunkel T. A., Loeb L. A. On the fidelity of DNA replication. Effect of divalent metal ion activators and deoxyrionucleoside triphosphate pools on in vitro mutagenesis. J Biol Chem. 1979 Jul 10;254(13):5718–5725. [PubMed] [Google Scholar]
  17. Kunz B. A., Barclay B. J., Game J. C., Little J. G., Haynes R. H. Induction of mitotic recombination in yeast by starvation for thymine nucleotides. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6057–6061. doi: 10.1073/pnas.77.10.6057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lee M. Y., Tan C. K., Downey K. M., So A. G. Further studies on calf thymus DNA polymerase delta purified to homogeneity by a new procedure. Biochemistry. 1984 Apr 24;23(9):1906–1913. doi: 10.1021/bi00304a003. [DOI] [PubMed] [Google Scholar]
  19. Meuth M., L'Heureux-Huard N., Trudel M. Characterization of a mutator gene in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6505–6509. doi: 10.1073/pnas.76.12.6505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Meuth M. Sensitivity of a mutator gene in Chinese hamster ovary cell to deoxynucleoside triphosphate pool alterations. Mol Cell Biol. 1981 Jul;1(7):652–660. doi: 10.1128/mcb.1.7.652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nalbantoglu J., Goncalves O., Meuth M. Structure of mutant alleles at the aprt locus of Chinese hamster ovary cells. J Mol Biol. 1983 Jul 5;167(3):575–594. doi: 10.1016/s0022-2836(83)80099-0. [DOI] [PubMed] [Google Scholar]
  22. Nalbantoglu J., Hartley D., Phear G., Tear G., Meuth M. Spontaneous deletion formation at the aprt locus of hamster cells: the presence of short sequence homologies and dyad symmetries at deletion termini. EMBO J. 1986 Jun;5(6):1199–1204. doi: 10.1002/j.1460-2075.1986.tb04347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nalbantoglu J., Phear G., Meuth M. DNA sequence analysis of spontaneous mutations at the aprt locus of hamster cells. Mol Cell Biol. 1987 Apr;7(4):1445–1449. doi: 10.1128/mcb.7.4.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  25. Perry P. E. Induction of sister-chromatid exchanges (SCEs) by thymidine and the potentiation of mutagen-induced SCEs in Chinese hamster ovary cells. Mutat Res. 1983 May;109(2):219–229. doi: 10.1016/0027-5107(83)90048-9. [DOI] [PubMed] [Google Scholar]
  26. Potter C. G. Induction of polyploidy by concentrated thymidine. Exp Cell Res. 1971 Oct;68(2):442–448. doi: 10.1016/0014-4827(71)90171-6. [DOI] [PubMed] [Google Scholar]
  27. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  28. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Scheuermann R. H., Echols H. A separate editing exonuclease for DNA replication: the epsilon subunit of Escherichia coli DNA polymerase III holoenzyme. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7747–7751. doi: 10.1073/pnas.81.24.7747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Seno T., Ayusawa D., Shimizu K., Koyama H., Takeishi K., Hori T. Thymineless death and genetic events in mammalian cells. Basic Life Sci. 1985;31:241–263. doi: 10.1007/978-1-4613-2449-2_15. [DOI] [PubMed] [Google Scholar]
  31. Skarnes W., Bonin P., Baril E. Exonuclease activity associated with a multiprotein form of HeLa cell DNA polymerase alpha. Purification and properties of the exonuclease. J Biol Chem. 1986 May 15;261(14):6629–6636. [PubMed] [Google Scholar]
  32. Trudel M., Van Genechten T., Meuth M. Biochemical characterization of the hamster thy mutator gene and its revertants. J Biol Chem. 1984 Feb 25;259(4):2355–2359. [PubMed] [Google Scholar]
  33. Wang M. L., Stellwagen R. H., Goodman M. F. Evidence for the absence of DNA proofreading in HeLa cell nuclei. J Biol Chem. 1981 Jul 25;256(14):7097–7100. [PubMed] [Google Scholar]
  34. Wang T. S., Hu S. Z., Korn D. DNA primase from KB cells. Characterization of a primase activity tightly associated with immunoaffinity-purified DNA polymerase-alpha. J Biol Chem. 1984 Feb 10;259(3):1854–1865. [PubMed] [Google Scholar]
  35. Weinberg G., Ullman B., Martin D. W., Jr Mutator phenotypes in mammalian cell mutants with distinct biochemical defects and abnormal deoxyribonucleoside triphosphate pools. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2447–2451. doi: 10.1073/pnas.78.4.2447. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES