Volume 2, Issue 1

Original research papers

Radiobiology

KINETICS OF UV-INDUCED GENE AND STRUCTURAL MUTATIONS

Natalia Koltovaya, Alexandra Kokoreva, Natalia Shvaneva, Nadya Zhuchkina

Pages: 10-13

DOI: 10.21175/RadJ.2017.01.003

Received: 29 FEB 2016, Received revised: 29 APR 2016, Accepted: 8 MAY 2016, Published online: 20 APR 2017

To study the kinetics of UV-induced gene and chromosome mutations in the yeast S. cerevisiae, several genetic assays were used. We treated yeast cells with UV light of up to 130 J/m2. UV irradiation induced all types of base substitutions, although transitions — in particular, GC-AT events — were predominant. Frameshift mutations were induced at the same frequency as the base pair substitution GC-AT, while forward mutations in the CAN1 gene exceeded the more expressive base pair substitutions by about an order of magnitude. Chromosome mutations were the most efficient. The kinetic of the induced gene and chromosome mutations is represented by a linear-quadratic function. Such curves have been reported for UV mutagenesis in bacteria and they have been explained by the induction of SOS error-prone repair. Similar biphasic kinetics was described for yeast in our work. These data suggest the occurrence of several factors forming the mutagenic response of eukaryotic cells to UV light.
  1. D. X. Tishkoff, N. Filosi, G. M. Gaida, R. D. Kolodner, “A novel mutation avoidance mechanism dependent on S. cerevsiaie RAD27 is distinct from DNA mismatch repair,” Cell, vol.88, pp. 253-263, 1997.
    DOI: 10.1016/S0092-8674(00)81846-2
  2. T-M. Williams, R. M. Fabbri, J. W. Reeves, G. F. Crouse, “A new reversion assay for measuring all possible base pair substitutions in Saccharomyces cerevisiae,Genetics, vol. 170, pp. 1423-1426, 2005.
    DOI: 10.1534/genetics.105.042697
    PMid: 15911571
    PMCid: PMC1451166
  3. K. S. Lobachev, B. M. Shor, H. T. Tran, W. Taylor, J. D. Keen, M. Resnick, D. A. Gordenin, “Factors affecting inverted repeat stimulation of recombination and deletion in Saccharomyces cerevisiae,Genetics, vol. 148, pp. 1507-1524, 1998.
    PMid: 9560370
    PMCid: PMC1460095
  4. Y. Tsukamoto, J. Kato, H. Ikeda, “Effects of mutations of RAD50, RAD51, RAD52, and related genes on illegitimate recombination in Saccharomyces cerevisiae,Genetics, vol. 142, pp. 383-391, 1996.
    PMid: 8852838
    PMCid: PMC1206973
  5. A. B. Devin, T. Yu. Prosvirova, V. T. Peshekhonov, O. V. Chepurnaya, M. Ye. Smirnova, N. A. Koltovaya, E. N. Troitskaya, I. P. Arman, “The start gene CDC28 and the genetic stability of yeast,” Yeast, vol. 6, pp. 231-243, 1990.
    DOI: 10.1002/yea.320060308
    PMid: 2190433
  6. F. Sherman, G. R. Fink, J. B. Hicks, Laboratory Course Manual for Methods in Yeast Genetics, Cold Spring Harbor Laboratory New York, 1981.
  7. A. L. Abdulovic, S. Jinks-Robertson, “The in vivo characterization of translesion synthesis across UV-induced lesions in Saccharomyces cerevisiae: insights into Polζ and Polη-dependent frameshift mutagenesis,” Genetics, vol. 172, pp. 1487-1498, 2006.
    DOI: 10.1534/genetics.105.052480
    PMid: 16387871
    PMCid: PMC1456278
  8. J. H. Miller, “Mutagenic specificity of ultraviolet light,” J. Mol. Biol., vol. 182, pp. 45-65, 1985.
    DOI: 10.1016/0022-2836(85)90026-9
  9. R. M. Schaaper, R. L. Dunn, B. W. Glickman, “Mechanisms of ultraviolet-induced mutation. Mutational spectra in the Escherihia coli lacI gene for a wild-type and an excision-repair-deficient strain,” J. Mol. Biol., vol. 198, pp. 187-202, 1987.
    DOI: 10.1016/0022-2836(87)90305-6
  10. B. A. Kunz, M. K. Pierce, J. R. Mis, C. N. Giroux, “DNA sequence analysis of the mutational specificity of u.v. light in the SUP4-o gene of yeast,” Mutagenesis, vol. 2, pp. 445-453, 1987.
    DOI: 10.1093/mutage/2.6.445
    PMid: 2832698
  11. M. Radman, “Phenomenology of an inducible mutagenic DNA-repair pathway in Escherihia coli: SOS repair hypothesis,” in: Molecular and Environmental Aspects of Mutagenesis, M. Miller, ed., Springfield (IL), USA: Thomas, 1974, pp. 128-142.
  12. J. P. McDonald, A. S. Levin, R. Woodgate, “The Saccharomyces cerevisiae RAD30 gene, a homologue of Eschrihia coli dinB and umuC, is DNA damage inducible and functions in a novel error-free postreplication repair mechanism,” Genetics, vol. 147, pp. 1557-1568, 1997.
    PMid: 9409821
    PMCid: PMC1208331
  13. A. A. Roush, E. C. Suarez, E. C. Friedberg, M. Radman, W. Siede, “Deletion of the Saccharomyces cerevisiae gene RAD30 encoding an Escherihia coli DinB homolog confers UV radiation sensitivity and altered mutability,” Mol. Gen. Genet., vol. 257, pp. 686-692, 1998.
    DOI: 10.1007/s004380050698
    PMid: 9604893
  14. K. Madura, S. Prakash, L. Prakash, “Expression of the Saccharomyces cerevisiae DNA repair gene RAD6 that encodes a ubiquitin conjugating enzyme, increases in response to DNA damage and in meiosis but remains constant during the mitotic cell cycle,” Nucleic Acids Res., vol. 18, pp. 771-778, 1990.
    DOI: 10.1093/nar/18.4.771
    DOI: 2179869
    PMCid: PMC330326
  15. J. S. Jones, L. Prakash, “Transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD18 increase in UV irradiated cells and during meiosis but not during the mitotic cell cycle,” Nucleic Acids Res., vol. 19, pp. 893-898, 1991.
    DOI: 10.1093/nar/19.4.893
    PMid: 2017370
    PMCid: PMC333727