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Genetic control of metabolism of mutagenic purine base analogs 6-hydroxylaminopurine and 2-amino-6-hydroxylaminopurine in yeast Saccharomyces cerevisiae

  • Genetics of Microorganisms
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Abstract

We studied the effect of inactivation of genes, which control biosynthesis of inosine monophosphate (IMP) de novo and purine salvage and interconversion pathways, on sensitivity of yeast Saccharomyces cerevisiae to the mutagenic and toxic action of 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine (AHA). It was shown that the manifestation of HAP and AHA mutagenic properties depends on the action of enzyme adenine phosphoribosyltransferase encoded in yeast by APT1 gene. A blockade of any step of IMP biosynthesis, with the exception of the block mediated by inactivation of genes ADE16 and ADE17 leading to the accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), was shown to enhance yeast cell sensitivity to the HAP mutagenic effect; however, it does not affect the sensitivity to AHA. A block of conversion of IMP into adenosine monophosphate (AMP) causes hypersensitivity of yeast cells to the mutagenic action of HAP and to the toxic effect of HAP, AHA, and hypoxanthine. It is possible that this enhancement of sensitivity to HAP and AHA is due to changes in the pool of purines. We conclude that genes ADE12, ADE13, AAH1, and HAM1 controlling processes of purine salvage and interconversion in yeast, make the greatest contribution to the protection against the toxic and mutagenic action of the examined analogs. Possible mechanisms of HAP detoxication in bacteria, yeast, and humans are discussed.

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Authors and Affiliations

  1. Department of Genetics and Selection, St. Petersburg State University, St. Petersburg, 199034, Russia

    E. I. Stepchenkova, S. G. Kozmin & V. V. Alenin

  2. St. Petersburg Branch, Vavilov Institute of General Genetics, Russian Academy of Sciences, St. Petersburg, 199034, Russia

    E. I. Stepchenkova

  3. National Institute of Environmental Health Sciences, RTP, NC, 27709, USA

    S. G. Kozmin

  4. Eppley Institute for Research in Cancer, 985880 University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Yu. I. Pavlov

Authors
  1. E. I. Stepchenkova
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  2. S. G. Kozmin
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  3. V. V. Alenin
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  4. Yu. I. Pavlov
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Correspondence to E. I. Stepchenkova.

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Original Russian Text © E.I. Stepchenkova, S.G. Kozmin, V.V. Alenin, Yu.I. Pavlov, 2009, published in Genetika, 2009, Vol. 45, No. 4, pp. 471–477.

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Stepchenkova, E.I., Kozmin, S.G., Alenin, V.V. et al. Genetic control of metabolism of mutagenic purine base analogs 6-hydroxylaminopurine and 2-amino-6-hydroxylaminopurine in yeast Saccharomyces cerevisiae . Russ J Genet 45, 409–414 (2009). https://doi.org/10.1134/S1022795409040048

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  • DOI: https://doi.org/10.1134/S1022795409040048

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