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Dot1 and Set2 histone methylases control the spontaneous and UV-induced mutagenesis levels in the Saccharomyces cerevisiae yeasts

  • Genetics of Microorganisms
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Abstract

In the Saccharomyces cerevisiae yeasts, the DOT1 gene product provides methylation of lysine 79 (K79) of histone H3 and the SET2 gene product provides the methylation of lysine 36 (K36) of the same histone. We determined that the dot1 and set2 mutants suppress the UV-induced mutagenesis to an equally high degree. The dot1 mutation demonstrated statistically higher sensitivity to the low doses of MMC than the wild type strain. The analysis of the interaction between the dot1 and rad52 mutations revealed a considerable level of spontaneous cell death in the double dot1 rad52 mutant. We observed strong suppression of the gamma-induced mutagenesis in the set2 mutant. We determined that the dot1 and set2 mutations decrease the spontaneous mutagenesis rate in both single and double mutants. The epistatic interaction between the dot1 and set2 mutations and almost similar sensitivity of the corresponding mutants to the different types of DNA damage allow one to conclude that both genes are involved in the control of the same DNA repair pathways, the homologous-recombination-based and the postreplicative DNA repair.

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References

  1. van Leeuwen, F., Gafken, P.R., and Gottschling, D.E., Dot1p modulates silencing in yeast by methylation of the nucleosome core, Cell, 2002, vol. 109, pp. 745–756.

    Article  CAS  PubMed  Google Scholar 

  2. Game, J.C., Williamson, M.S., and Baccari, C., X-ray survival characteristics and genetic analysis for nine Saccharomyces deletion mutants that show altered radiation sensitivity, Genetics, 2005, vol. 169, pp. 51–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Game, J.C., Williamson, M.S., Spicakova, T., and Brown, J.M., The RAD6/BRE1 histone modification pathway in Saccharomyces cerevisiae confers radiation resistance through a RAD51-dependent process that is independent of RAD18, Genetics, 2006, vol. 173, pp. 1951–1968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Grenon, M., Costelloe, T., Jimeno, S., et al., Docking onto chromatin via the Saccharomyces cerevisiae Rad9 Tudor domain, Yeast, 2007, vol. 24, pp. 105–119.

    Article  CAS  PubMed  Google Scholar 

  5. Chaudhuri, S., Wyrick, J.J., and Smerdon, M.J., Histone H3 Lys79 methylation is required for efficient nucleotide excision repair in a silenced locus of Saccharomyces cerevisiae, Nucleic Acids Res., 2009, vol. 37, pp. 1690–1700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Huyen, Y., Zgheib, O., Ditullio, R.A., Jr., et al., Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks, Nature, 2004, vol. 432, pp. 406–411.

    Article  CAS  PubMed  Google Scholar 

  7. Bostelman, L.J., Keller, A.M., Albrecht, A.M., et al., Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae, DNA Repair, 2007, vol. 6, pp. 383–395.

    Article  CAS  PubMed  Google Scholar 

  8. Conde, F. and San-Segundo, P.A., Role of Dot1 in the response to alkylating DNA damage in Saccharomyces cerevisiae: regulation of DNA damage tolerance by the error-prone polymerases Polzeta/Rev1, Genetics, 2008, vol. 179, pp. 1197–1210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. San-Segundo, P.A. and Roeder, G.S., Role for the silencing protein Dot1 in meiotic checkpoint control, Mol. Biol. Cell, 2000, vol. 11, pp. 3601–3615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wysocki, R., Javaheri, A., Allard, S., et al., Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9, Mol. Cell. Biol., 2005, vol. 25, pp. 8430–8443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ng, H.H., Xu, R.M., Zhang, Y., and Struhl, K., Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone 3 lysine 79, J. Biol. Chem., 2002, vol. 277, pp. 34655–34657.

    Article  CAS  PubMed  Google Scholar 

  12. Briggs, S.D., Xiao, T., Sun, Z.W., et al., Gene silencing: trans-histone regulatory pathway in chromatin, Nature, 2002, vol. 418, p. 498.

    Article  CAS  PubMed  Google Scholar 

  13. Dover, J., Schneider, J., Tawiah-Boateng, M.A., et al., Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6, J. Biol. Chem., 2002, vol. 277, pp. 28368–28371.

    Article  CAS  PubMed  Google Scholar 

  14. Shahbazian, M.D., Zhang, K., and Grunstein, M., Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1, Mol. Cell, 2005, vol. 19, pp. 271–277.

    Article  CAS  PubMed  Google Scholar 

  15. Lee, J.S., Shukla, A., Schneider, J., et al., Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS, Cell, 2007, vol. 131, pp. 1084–1096.

    Article  CAS  PubMed  Google Scholar 

  16. Game, J.C. and Mortimer, R.K., A genetic study of X-ray sensitive mutants in yeast, Mutat. Res., 1974, vol. 24, pp. 281–292.

    Article  CAS  PubMed  Google Scholar 

  17. Giannattasio, M., Lazzaro, F., Plevani, P., and MuziFalconi, M., The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1, J. Biol. Chem., 2005, vol. 280, pp. 9879–9886.

    Article  CAS  PubMed  Google Scholar 

  18. Robzyk, K., Recht, J., and Osley, M.A., Rad6-dependent ubiquitination of histone H2B in yeast, Science, 2000, vol. 287, pp. 501–504.

    Article  CAS  PubMed  Google Scholar 

  19. Hwang, W.W., Venkatasubrahmanyam, S., Ianculescu, A.G., et al., A conserved ring finger protein required for histone H2B monoubiquitination and cell size control, Mol. Cell, 2003, vol. 11, pp. 261–266.

    Article  CAS  PubMed  Google Scholar 

  20. Wood, A., Krogan, N.J., Dover, J., et al., Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter, Mol. Cell, 2003, vol. 11, pp. 267–274.

    CAS  Google Scholar 

  21. Krogan, N.J., Keogh, M.C., Datta, N., et al., A Snf2 family ATPase complex required for recruitment of the histone H2A variant Htz1, Mol. Cell, 2003, vol. 12, pp. 1565–1576.

    Article  CAS  PubMed  Google Scholar 

  22. Ng, H.H., Dole, S., and Struhl, K., The Rtf1 component of the Paf1 transcriptional elongation complex is required for ubiquitination of histone H2B, J. Biol. Chem., 2003, vol. 278, pp. 33625–33628.

    Article  CAS  PubMed  Google Scholar 

  23. Lis, E.T. and Romesherg, F.E., Role of Doa1 in the Saccharomyces cerevisiae DNA damage response, Mol. Cell. Biol., 2006, vol. 26, pp. 4123–4133.

    Article  Google Scholar 

  24. Strahl, B.D., Grant, P.A., Briggs, S.D., et al., Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression, Mol. Cell. Biol., 2002, vol. 22, pp. 1298–1306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sanders, S.L., Portoso, M., Mata, J., et al., Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage, Cell, 2004, vol. 119, pp. 603–614.

    Article  CAS  PubMed  Google Scholar 

  26. Krogan, N.J., Kim, M., Tong, A., et al., Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II, Mol. Cell. Biol., 2003, vol. 23, pp. 4207–4218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li, B., Howe, L., Anderson, S., Yates, J.R. III, and Workman, J.L., The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase II, J. Biol. Chem., 2003, vol. 8897–8903.

    Google Scholar 

  28. Xiao, T., Hall, H., Kizer, K.O., et al., Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast, Genes Dev., 2003, vol. 17, pp. 654–663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rao, B., Shibata, Y., Strahl, B.D., and Lieb, J.D., Dimethylation of histone H3 at lysine 36 demarcates regulatory and nonregulatory chromatin genome-wide, Mol. Cell. Biol., 2007, vol. 27, pp. 721–731.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zakharov, I.A., Kozhin, S.A., Kozhina, T.A., and Fedorova, I.V., Sbornik metodik po genetike drozhzheisakharomitsetov, (Methods in Yeast Saccharomyces cerevisiae Genetics), Leningrad: Nauka, 1984.

    Google Scholar 

  31. Koval’tsova, S.V. and Korolev, V.G., The Saccharomyces cerevisiae yeast strain for testing environmental mutagens based on the interaction between rad2 and him1 mutations, Russ. J. Genet., 1996, vol. 32, no. 3, pp. 366–372.

    Google Scholar 

  32. Roman, H., A system selective for mutations affecting the synthesis of adenine in yeast, Compt. Rend. Trav. Lab. Carlsberg, Ser. Physiol., 1956, vol. 26, pp. 299–314.

    CAS  Google Scholar 

  33. Khromov-Borisov, N.N., Saffi, J., and Henriques, J.A.P., Perfect order plating: principal and applications, TTO, 2002, vol. 1, p. TO2638.

  34. Lea, D.E. and Coulson, C.A., The distribution of the number of mutants in bacterial populations, J. Genet., 1949, vol. 49, pp. 264–285.

    Article  CAS  PubMed  Google Scholar 

  35. Conde, F., Ontoso, D., Acosta, I., et al., Regulation of tolerance to DNA alkylating damage by Dot1 and Rad53 in Saccharomyces cerevisiae, DNA Repair, 2010, vol. 9, pp. 1038–1049.

    Article  CAS  PubMed  Google Scholar 

  36. Chabes, A., Georgieva, D., Domkin, V., et al., Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase, Cell, 2003, vol. 112, pp. 391–401.

    Article  CAS  PubMed  Google Scholar 

  37. Jordan, A. and Reichard, P., Ribonucleotide reductases, Annu. Rev. Biochem., 1998, vol. 67, pp. 71–98.

    Article  CAS  PubMed  Google Scholar 

  38. Reichard, P., Interactions between deoxyribonucleotide and DNA synthesis, Annu. Rev. Biochem., 1988, vol. 57, pp. 349–374.

    Article  CAS  PubMed  Google Scholar 

  39. Elledge, S.J. and Davis, R.W., Identification and isolation of the gene encoding the small subunit of ribonucleotide reductase from Saccharomyces cerevisiae: DNA damage-inducible gene required for mitotic viability, Mol. Cell. Biol., 1987, vol. 7, pp. 2783–2793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Elledge, S.J. and Davis, R.W., Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase, Genes Dev., 1990, vol. 4, pp. 740–751.

    Article  CAS  PubMed  Google Scholar 

  41. Huang, M. and Elledge, S.J., Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae, Mol. Cell. Biol., 1997, vol. 17, pp. 6105–6113.

    CAS  PubMed  Google Scholar 

  42. Wang, P.J., Chabes, A., Casagrande, R., et al., Rnr4p, a novel ribonucleotide reductase small-subunit protein, Mol. Cell. Biol., 1997, vol. 17, pp. 6114–6121.

    CAS  PubMed  Google Scholar 

  43. Zhou, Z. and Elledge, S.J., DUN1 encodes a protein kinase that controls the DNA damage response in yeast, Cell, 1989, vol. 75, pp. 1119–1127.

    Article  Google Scholar 

  44. Zhao, X., Miller, E.G., and Rothstein, R., A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools, Mol. Cell, 1998, vol. 2, pp. 329–340.

    Article  CAS  PubMed  Google Scholar 

  45. Chabes, A., Domkin, V., and Thelander, L., Yeast Sml1, a protein inhibitor of ribonucleotide reductase, J. Biol. Chem., 1999, vol. 274, pp. 36679–36683.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Konstantinov Petersburg Nuclear Physics Institute, National Research Center Kurchatov Institute, St. Petersburg, Gatchina, Leningrad oblast, 188300, Russia

    T. N. Kozhina, T. A. Evstiukhina, V. T. Peshekhonov, A. Yu. Chernenkov & V. G. Korolev

  2. Department of Biophysics, Institute of Physics, Nanotechnology, and Telecommunications, St. Petersburg State Polytechnic University, St. Petersburg, 195251, Russia

    T. N. Kozhina

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  1. T. N. Kozhina
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  2. T. A. Evstiukhina
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  5. V. G. Korolev
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Correspondence to T. N. Kozhina.

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Original Russian Text © T.N. Kozhina, T.A. Evstiukhina, V.T. Peshekhonov, A.Yu. Chernenkov, V.G. Korolev, 2016, published in Genetika, 2016, Vol. 52, No. 3, pp. 300–310.

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Kozhina, T.N., Evstiukhina, T.A., Peshekhonov, V.T. et al. Dot1 and Set2 histone methylases control the spontaneous and UV-induced mutagenesis levels in the Saccharomyces cerevisiae yeasts. Russ J Genet 52, 263–272 (2016). https://doi.org/10.1134/S102279541602006X

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  • DOI: https://doi.org/10.1134/S102279541602006X

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