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Gene Review

DOT1  -  Dot1p

Saccharomyces cerevisiae S288c

Synonyms: D9461.26, Disrupter of telomere silencing protein 1, H3-K79-HMTase, Histone H3-K79 methyltransferase, Histone-lysine N-methyltransferase, H3 lysine-79 specific, ...
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High impact information on DOT1

  • Dot1p modulates silencing in yeast by methylation of the nucleosome core [1].
  • We now find that Dot1p methylates histone H3 on lysine 79, which maps to the top and bottom of the nucleosome core [1].
  • The side chains, identified from mutants in which all three forms of silencing (rDNA, telomere and silent mating locus silencing) are eliminated, are centered around Lys79 of histone H3, a residue methylated by the yeast Dot1 protein [2].
  • This defect in telomeric silencing might reflect an interaction between Sir proteins and Lys 79, because dot1 and Lys 79 mutations weaken the interaction of Sir2 and Sir3 with the telomeric region in vivo [3].
  • Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1 [4].

Biological context of DOT1

  • In the absence of DOT1, the zip1 and dmc1 mutants inappropriately progress through meiosis, generating inviable meiotic products [5].
  • DOT1 deletion also affected telomere tract length [6].
  • In addition to its checkpoint function, Dot1 blocks the repair of meiotic double-strand breaks by a Rad54-dependent pathway of recombination between sister chromatids [5].
  • We screened radiation-sensitive yeast mutants for DNA damage checkpoint defects and identified Dot1, the conserved histone H3 Lys 79 methyltransferase [7].
  • Methylation of histone H3 on lysines 4 and 79, catalyzed by the Set1-containing complex COMPASS and Dot1p, respectively, is required for silencing of expression of genes located near chromosome telomeres in yeast [8].

Associations of DOT1 with chemical compounds

  • The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein [9].
  • We document the divalent cation dependence and specificity of SpCdk9/Pch1, its NTP dependence and specificity, the dependence of Spt5-CTD phosphorylation on the number of tandem nonamer repeats, and the specificity for phosphorylation of the Spt5-CTD on threonine at position 1 within the nonamer element [10].
  • The elongated structure of the conserved core of yeast Dot1p contains an N-terminal helical domain and a seven-stranded catalytic domain that harbors the binding site for the methyl-donor and an active site pocket sided with conserved hydrophobic residues [11].

Physical interactions of DOT1


Enzymatic interactions of DOT1


Other interactions of DOT1

  • In vegetative cells, mutation of DOT1 results in delocalization of Sir3 from telomeres, accounting for the impaired telomeric silencing in dot1 [5].
  • Our results show that RAD9 is epistatic to DOT1 and suggest that it acts downstream of the Dot1 methylase in the damage resistance and checkpoint response [12].
  • Moreover, deletion of the latter two genes weakened silencing as well, suggesting that DOT1 and DOT4 normally play important roles in gene repression [6].
  • This type of induction was observed only in the absence of SET1 and not in the absence of other histone methyltransferases, SET2 or DOT1 [13].
  • Characterization of the Schizosaccharomyces pombe Cdk9/Pch1 protein kinase: Spt5 phosphorylation, autophosphorylation, and mutational analysis [10].


  1. Dot1p modulates silencing in yeast by methylation of the nucleosome core. van Leeuwen, F., Gafken, P.R., Gottschling, D.E. Cell (2002) [Pubmed]
  2. A core nucleosome surface crucial for transcriptional silencing. Park, J.H., Cosgrove, M.S., Youngman, E., Wolberger, C., Boeke, J.D. Nat. Genet. (2002) [Pubmed]
  3. Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Ng, H.H., Feng, Q., Wang, H., Erdjument-Bromage, H., Tempst, P., Zhang, Y., Struhl, K. Genes Dev. (2002) [Pubmed]
  4. Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1. Shahbazian, M.D., Zhang, K., Grunstein, M. Mol. Cell (2005) [Pubmed]
  5. Role for the silencing protein Dot1 in meiotic checkpoint control. San-Segundo, P.A., Roeder, G.S. Mol. Biol. Cell (2000) [Pubmed]
  6. Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae. Singer, M.S., Kahana, A., Wolf, A.J., Meisinger, L.L., Peterson, S.E., Goggin, C., Mahowald, M., Gottschling, D.E. Genetics (1998) [Pubmed]
  7. Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Wysocki, R., Javaheri, A., Allard, S., Sha, F., Côté, J., Kron, S.J. Mol. Cell. Biol. (2005) [Pubmed]
  8. The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. Krogan, N.J., Dover, J., Wood, A., Schneider, J., Heidt, J., Boateng, M.A., Dean, K., Ryan, O.W., Golshani, A., Johnston, M., Greenblatt, J.F., Shilatifard, A. Mol. Cell (2003) [Pubmed]
  9. X-ray survival characteristics and genetic analysis for nine Saccharomyces deletion mutants that show altered radiation sensitivity. Game, J.C., Williamson, M.S., Baccari, C. Genetics (2005) [Pubmed]
  10. Characterization of the Schizosaccharomyces pombe Cdk9/Pch1 protein kinase: Spt5 phosphorylation, autophosphorylation, and mutational analysis. Pei, Y., Shuman, S. J. Biol. Chem. (2003) [Pubmed]
  11. Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase. Sawada, K., Yang, Z., Horton, J.R., Collins, R.E., Zhang, X., Cheng, X. J. Biol. Chem. (2004) [Pubmed]
  12. Docking onto chromatin via the Saccharomyces cerevisiae Rad9 Tudor domain. Grenon, M., Costelloe, T., Jimeno, S., O'shaughnessy, A., Fitzgerald, J., Zgheib, O., Degerth, L., Lowndes, N.F. Yeast (2007) [Pubmed]
  13. Different roles of histone H3 lysine 4 methylation in chromatin maintenance. Seol, J.H., Kim, H.J., Yang, Y.J., Kim, S.T., Youn, H.D., Han, J.W., Lee, H.W., Cho, E.J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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