All Types of Base Pair Substitutions Induced by γ-Rays in Haploid and Diploid Yeast Cells
We study the biological effects induced by ionizing radiation in view of therapeutic exposure and the idea of space flights beyond Earth's magnetosphere. In particular, we examine the differences between base pair substitution induction by ionizing radiation in model haploid and diploid yeast Saccharomyces cerevisiae cells. Such mutations are difficult to study in higher eukaryotic systems. In our research, we have used a collection of six isogenic trp5-strains and 14 isogenic haploid and diploid cyc1-strains that are specific markers of all possible base-pair substitutions. These strains differ from each other only in single base substitutions within codon-50 of the trp5 gene or codon-22 of the cyc1 gene. Different mutation spectra for two different haploid genetic trp5- and cyc1-assays and different mutation spectra for the same genetic cyc1-system in cells with different ploidy — haploid and diploid — have been obtained. It was linear function for dose-dependence in haploid and exponential in diploid cells. We suggest that the differences between haploid yeast strains reflect the dependence on the sequence context, while the differences between haploid and diploid strains reflect the different molecular mechanisms of mutations.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1474453Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 280
 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.
 T.-M. Williams, R. M. Fabbri, J. W. Reeves, G. F. Crouse, “A new reversion assay for measuring all possible base pair substitutions in S. cerevisiae”, Genetics, vol. 170, pp. 1423-1426, 2005.
 M. Hampsey, “A tester system for detecting each of the six base-pair substitutions in Saccahromyces cerevisiae by selecting for an essential cysteine in iso-1-cytochrome c”, Genetics, vol. 128, pp. 59-67, 1991.
 N. N. Khromov-Borisov, J. Saffi, J. A. P. Henriques, “Perfect order plating: principal and applications”, Technical Tips Online, vol. 6, pp. 51-57, 2001.
 R. Mortimer, T. Brustad, D. Cormak, “Influence of linear energy transfer and oxygen tension on the effectiveness of ionizing radiation for induction of mutations and lethality in Saccharomyces cerevisiae”, Radiation Research, vol. 26, pp. 465-482, 1965.
 K. A. Lyubimova, S. A. Anikin, N. A. Koltovay, E. A. Krasavin, “Requlariries of the induction of point mutations in the yeast Saccahromyces cerevisiae after exposure to γ-radiation”, Genetika (Rus.), vol. 34, pp. 1228-1232, 1998.
 Y. Nakabeppu, K. Sakumi, K. Sakumoto, D. Tsuchimoto, T. Tsuzuki, Y. Nakatsu, “Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids”, Journal of Biological Chemistry, vol. 387, pp. 373-379, 2006.
 D. I. Feig, L. A. Loeb, “Mechanism of mutation by oxidative DNA damage: reduced fidelity of mammalian DNA polymerase-β”, Biochemistry, vol. 32, pp. 4466-4473, 1993.
 F. Yuan, Y. Zhang, D. Rajpal, X. Wu, D. Guo, M. Wang. J.-S. Taylor, Z. Wang, “Specificity of DNA lesion bypass by the yeast DNA polymerase η”, Journal of Biological Chemistry, vol. 275, pp. 8233-8239, 2000.
 J. R. Nelson, C. W. Lawrence, D. C. Hinkle, “Deoxycytidyl transferase activity of yeast REV1 protein”, Nature, vol. 382, pp. 729-731, 1996.
 R. E. Johnson, C. A. Torre-Ramos, T. Izumi, S. Mitra, S. Prakash, I. Prakash, “Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites”, Genes Development, vol. 12, pp. 3137-3143, 1998.
 J. P. McDonald, A. S. Levin, R. Woodgate, “The Saccharomyces cerevisiae RAD30 gene, a homologue of Escherichia 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.
 A. A. Roush, M. Suarez, E. C. Friedberg, M. Radman, W. Siede, “Deletion of the Saccharomyces cerevisiae gene RAD30 encoding an Escherichia coli DinB homolog confers UV radiation sensitivity and altered mutability”, Molecular and General Genetics, vol. 257, pp. 686-692, 1998.
 M. Moriya, “Single-strand shuttle phagemid for mutagenesis studies in mammalian cells: 8-Oxoguanine in DNA induces targeted GC-TA transversions in simian kidney cells”, Proc. Natl. Acad. Sci. USA, vol. 90, pp. 1122-1126, 1993.
 W. M. Hick, M. Kim, J. E. Haber, “Increased mutagenesis and unique mutation signature associated with mitotic gene conversion”, Science, vol. 329, pp. 82-85, 2010.
 L. H. Burch, Y. Yang, J. F. Sterling, S. A. Roberts, F. G. Chao, H. Xu, L. Zhang, J. Walsh, M. A. Resnick, P. A. Mieczkowski, D. A. Gordenin, “Damage-induced localized hypermutability”, Cell Cycle, vol. 10, pp. 1073-1085, 2011.