Gene Symbol: DOT1
Description: histone methyltransferase DOT1
Alias: KMT4, PCH1, histone methyltransferase DOT1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Rossmann M, Luo W, Tsaponina O, Chabes A, Stillman B. A common telomeric gene silencing assay is affected by nucleotide metabolism. Mol Cell. 2011;42:127-36 pubmed publisher
    ..For two genes implicated in telomere silencing, POL30 and DOT1, we show that the URA3 telomere reporter assay does not reflect their role in heterochromatin formation...
  2. Foster E, Downs J. Methylation of H3 K4 and K79 is not strictly dependent on H2B K123 ubiquitylation. J Cell Biol. 2009;184:631-8 pubmed publisher
    ..Finally, we show that strains lacking the ubiquitin ligase Bre1 are defective for H3 methylation, suggesting that there is an additional Bre1 substrate that in combination with H2B K123 facilitates H3 methylation. ..
  3. Takahashi Y, Schulze J, Jackson J, Hentrich T, Seidel C, Jaspersen S, et al. Dot1 and histone H3K79 methylation in natural telomeric and HM silencing. Mol Cell. 2011;42:118-26 pubmed publisher
    ..located at TEL-VII-L of Saccharomyces cerevisiae, it was proposed that the disruptor of telomeric silencing-1 (Dot1) regulates TPEV by catalyzing H3K79 methylation...
  4. Conde F, San Segundo P. 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;179:1197-210 pubmed publisher
    ..b>Dot1 methylates lysine 79 of histone H3...
  5. Frederiks F, Tzouros M, Oudgenoeg G, van Welsem T, Fornerod M, Krijgsveld J, et al. Nonprocessive methylation by Dot1 leads to functional redundancy of histone H3K79 methylation states. Nat Struct Mol Biol. 2008;15:550-7 pubmed publisher
    ..have been attributed so far to the different methylation states of histone H3 Lysine 79 (H3K79) generated by Dot1. Here we show that Dot1, in contrast to other known histone methyltransferases, introduces multiple methyl groups ..
  6. Lazzaro F, Sapountzi V, Granata M, Pellicioli A, Vaze M, Haber J, et al. Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres. EMBO J. 2008;27:1502-12 pubmed publisher
    ..Loss of DOT1 or mutations in RAD9 influence a Rad50-dependent nuclease, leading to more rapid accumulation of ssDNA, and faster ..
  7. Bostelman L, Keller A, Albrecht A, Arat A, Thompson J. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae. DNA Repair (Amst). 2007;6:383-95 pubmed
    ..We find that a dot1 null mutation and a histone H3 point mutation at lysine-79 cause increased sensitivity to UV radiation, suggesting ..
  8. Ontoso D, Acosta I, van Leeuwen F, Freire R, San Segundo P. Dot1-dependent histone H3K79 methylation promotes activation of the Mek1 meiotic checkpoint effector kinase by regulating the Hop1 adaptor. PLoS Genet. 2013;9:e1003262 pubmed publisher
    ..Here, we unveil the role of Dot1-dependent histone H3 methylation at lysine 79 (H3K79me) in this meiotic surveillance mechanism...
  9. van Welsem T, Frederiks F, Verzijlbergen K, Faber A, Nelson Z, Egan D, et al. Synthetic lethal screens identify gene silencing processes in yeast and implicate the acetylated amino terminus of Sir3 in recognition of the nucleosome core. Mol Cell Biol. 2008;28:3861-72 pubmed publisher
    b>Dot1 methylates histone H3 lysine 79 (H3K79) on the nucleosome core and is involved in Sir protein-mediated silencing...

More Information


  1. Altaf M, Utley R, Lacoste N, Tan S, Briggs S, Cote J. Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin. Mol Cell. 2007;28:1002-14 pubmed
    b>Dot1 (Disruptor of telomeric silencing-1) is a histone H3 lysine 79 methyltransferase that contributes to the establishment of heterochromatin boundary and has been linked to transcription elongation...
  2. Ng H, Feng Q, Wang H, Erdjument Bromage H, Tempst P, Zhang Y, et al. Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes Dev. 2002;16:1518-27 pubmed
    ..In the yeast Saccharomyces cerevisiae, Lys 79 of histone H3 is methylated by Dot1, a protein shown previously to play a role in telomeric silencing...
  3. Nakanishi S, Lee J, Gardner K, Gardner J, Takahashi Y, Chandrasekharan M, et al. Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1. J Cell Biol. 2009;186:371-7 pubmed publisher
    ..monoubiquitination by Rad6/Bre1 is required for the trimethylation of both histone H3K4 and H3K79 by COMPASS and Dot1 methyltransferases, respectively...
  4. Conde F, Refolio E, Cordon Preciado V, Cortes Ledesma F, Aragon L, Aguilera A, et al. The Dot1 histone methyltransferase and the Rad9 checkpoint adaptor contribute to cohesin-dependent double-strand break repair by sister chromatid recombination in Saccharomyces cerevisiae. Genetics. 2009;182:437-46 pubmed publisher
    ..Here, we study the role of the histone H3K79 methyltransferase Dot1 in the repair by SCR of replication-dependent HO-induced DSBs, as a way to assess its function in homologous ..
  5. Puddu F, Granata M, di Nola L, Balestrini A, Piergiovanni G, Lazzaro F, et al. Phosphorylation of the budding yeast 9-1-1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint. Mol Cell Biol. 2008;28:4782-93 pubmed publisher
    ..In budding yeast, methylated H3-K79 is bound by the checkpoint factor Rad9. Loss of Dot1 prevents H3-K79 methylation, leading to a checkpoint defect in the G(1) phase of the cell cycle and to a reduction ..
  6. Giannattasio M, Lazzaro F, Plevani P, Muzi Falconi M. The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J Biol Chem. 2005;280:9879-86 pubmed
    ..We found a similar requirement for Dot1-dependent methylation of histone H3...
  7. Lacoste N, Utley R, Hunter J, Poirier G, Cote J. Disruptor of telomeric silencing-1 is a chromatin-specific histone H3 methyltransferase. J Biol Chem. 2002;277:30421-4 pubmed
    Yeast disruptor of telomeric silencing-1 (DOT1) is involved in gene silencing and in the pachytene checkpoint during meiotic cell cycle. Here we show that the Dot1 protein possesses intrinsic histone methyltransferase (HMT) activity...
  8. Evans M, Bostelman L, Albrecht A, Keller A, Strande N, Thompson J. UV sensitive mutations in histone H3 in Saccharomyces cerevisiae that alter specific K79 methylation states genetically act through distinct DNA repair pathways. Curr Genet. 2008;53:259-74 pubmed publisher
  9. Game J, Williamson M, Spicakova T, Brown J. The RAD6/BRE1 histone modification pathway in Saccharomyces confers radiation resistance through a RAD51-dependent process that is independent of RAD18. Genetics. 2006;173:1951-68 pubmed
    ..We conclude that IR resistance conferred by BRE1 and DOT1 is mediated through homologous recombinational repair, not postreplication repair, and confirm findings of a G1 ..
  10. San Segundo P, Roeder G. Role for the silencing protein Dot1 in meiotic checkpoint control. Mol Biol Cell. 2000;11:3601-15 pubmed
    ..The silencing protein Dot1 (also known as Pch1) is required for checkpoint-mediated pachytene arrest of the zip1 and dmc1 mutants of Saccharomyces cerevisiae...
  11. van Leeuwen F, Gafken P, Gottschling D. Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell. 2002;109:745-56 pubmed
    b>DOT1 was originally identified as a gene affecting telomeric silencing in S. cerevisiae. We now find that Dot1p methylates histone H3 on lysine 79, which maps to the top and bottom of the nucleosome core...
  12. Tatum D, Li S. Evidence that the histone methyltransferase Dot1 mediates global genomic repair by methylating histone H3 on lysine 79. J Biol Chem. 2011;286:17530-5 pubmed publisher
    ..b>Dot1, a histone methyltransferase required for methylation of histone H3 lysine 79 (H3K79), has been shown to confer ..
  13. Lévesque N, Leung G, Fok A, Schmidt T, Kobor M. Loss of H3 K79 trimethylation leads to suppression of Rtt107-dependent DNA damage sensitivity through the translesion synthesis pathway. J Biol Chem. 2010;285:35113-22 pubmed publisher
    ..Further analysis revealed that lack of Dot1, the H3 K79 methyltransferase, led to activation of the translesion synthesis pathway, thereby allowing the ..
  14. Conde F, Ontoso D, Acosta I, Gallego Sánchez A, Bueno A, San Segundo P. Regulation of tolerance to DNA alkylating damage by Dot1 and Rad53 in Saccharomyces cerevisiae. DNA Repair (Amst). 2010;9:1038-49 pubmed publisher
    ..Here, we investigate the functional contribution of the Dot1 histone methyltransferase and the Rad53 checkpoint kinase to TLS regulation in Saccharomyces cerevisiae...
  15. Wysocki R, Javaheri A, Allard S, Sha F, Cote J, Kron S. Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Mol Cell Biol. 2005;25:8430-43 pubmed
    We screened radiation-sensitive yeast mutants for DNA damage checkpoint defects and identified Dot1, the conserved histone H3 Lys 79 methyltransferase...
  16. Cavero S, Herruzo E, Ontoso D, San Segundo P. Impact of histone H4K16 acetylation on the meiotic recombination checkpoint in Saccharomyces cerevisiae. Microb Cell. 2016;3:606-620 pubmed publisher
    ..Meiotic recombination occurs in the context of chromatin; in fact, the histone methyltransferase Dot1 and the histone deacetylase Sir2 are known regulators of the pachytene checkpoint in Saccharomyces ..
  17. Ezhkova E, Tansey W. Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3. Mol Cell. 2004;13:435-42 pubmed
    ..These data reveal that proteasome subunits function in epigenetic gene regulation by linking chromatin modifications that establish the histone code. ..
  18. Pfander B, Diffley J. Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. EMBO J. 2011;30:4897-907 pubmed publisher
    ..Thus, Dpb11 coordinates checkpoint signal transduction both temporally and spatially, ensuring the initiator kinase is specifically activated in proximity of one of its critical substrates. ..
  19. Frederiks F, Heynen G, van Deventer S, Janssen H, van Leeuwen F. Two Dot1 isoforms in Saccharomyces cerevisiae as a result of leaky scanning by the ribosome. Nucleic Acids Res. 2009;37:7047-58 pubmed publisher
    b>Dot1 is a conserved histone methyltransferase that methylates histone H3 on lysine 79. We previously observed that in Saccharomyces cerevisiae, a single DOT1 gene encodes two Dot1 protein species...
  20. Jablonowski C, Cussiol J, Oberly S, Yimit A, Balint A, Kim T, et al. Termination of Replication Stress Signaling via Concerted Action of the Slx4 Scaffold and the PP4 Phosphatase. Genetics. 2015;201:937-49 pubmed publisher
    ..We propose that the proper spatial coordination of the Slx4 scaffold and PP4 action is crucial to allow timely activation of Mus81-Mms4 and, therefore, proper chromosome segregation. ..
  21. Gritenaite D, Princz L, Szakal B, Bantele S, Wendeler L, Schilbach S, et al. A cell cycle-regulated Slx4-Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication. Genes Dev. 2014;28:1604-19 pubmed publisher
    ..Thus, Dpb11-Slx4 integrates several cellular inputs and participates in the temporal program for activation of the JM-resolving nuclease Mus81. ..
  22. Oh S, Jeong K, Kim H, Kwon C, Lee D. A lysine-rich region in Dot1p is crucial for direct interaction with H2B ubiquitylation and high level methylation of H3K79. Biochem Biophys Res Commun. 2010;399:512-7 pubmed publisher
    ..Taken together, our results indicate that a direct interaction between the lysine-rich region of Dot1p and the ubiquitin of H2Bub is required for H2Bub-mediated trans-tail regulation. ..
  23. Verzijlbergen K, Faber A, Stulemeijer I, van Leeuwen F. Multiple histone modifications in euchromatin promote heterochromatin formation by redundant mechanisms in Saccharomyces cerevisiae. BMC Mol Biol. 2009;10:76 pubmed publisher
    Methylation of lysine 79 on histone H3 by Dot1 is required for maintenance of heterochromatin structure in yeast and humans. However, this histone modification occurs predominantly in euchromatin...
  24. Osborne E, Dudoit S, Rine J. The establishment of gene silencing at single-cell resolution. Nat Genet. 2009;41:800-6 pubmed publisher
    ..unexpected complexity in the contributions of a histone acetyltransferase (Sas2), two histone methytransferases (Dot1 and Set1) and one histone demethylase (Jhd2) to the dynamics of silencing...
  25. Meng F, Hu Y, Shen N, Tong X, Wang J, Ding J, et al. Sua5p a single-stranded telomeric DNA-binding protein facilitates telomere replication. EMBO J. 2009;28:1466-78 pubmed publisher
    ..Thus, Sua5p represents a novel ssTG DNA-binding protein and positively regulates the telomere length in vivo. ..
  26. Mayor T, Graumann J, Bryan J, MacCoss M, Deshaies R. Quantitative profiling of ubiquitylated proteins reveals proteasome substrates and the substrate repertoire influenced by the Rpn10 receptor pathway. Mol Cell Proteomics. 2007;6:1885-95 pubmed
    ..This approach illustrates the feasibility of systems-level quantitative analysis to map enzyme-substrate networks in the UPS. ..
  27. Herruzo E, Ontoso D, González Arranz S, Cavero S, Lechuga A, San Segundo P. The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects. Nucleic Acids Res. 2016;44:7722-41 pubmed publisher
    ..Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. ..
  28. Najor N, Weatherford L, Brush G. Prevention of DNA Rereplication Through a Meiotic Recombination Checkpoint Response. G3 (Bethesda). 2016;6:3869-3881 pubmed publisher
    ..While this response is similar to a checkpoint mechanism that inhibits initiation of DNA replication in the mitotic cell cycle, the evidence points to a new variation on DNA replication control. ..
  29. Siler J, Xia B, Wong C, Kath M, Bi X. Cell cycle-dependent positive and negative functions of Fun30 chromatin remodeler in DNA damage response. DNA Repair (Amst). 2017;50:61-70 pubmed publisher
    ..These results indicate that both positive and negative functions of Fun30 in DNA damage response occur mainly in G2/M phase. ..
  30. Poon B, Mekhail K. Effects of Perinuclear Chromosome Tethers in the Telomeric URA3/5FOA System Reflect Changes to Gene Silencing and not Nucleotide Metabolism. Front Genet. 2012;3:144 pubmed publisher
    ..This is key to understanding relationships between telomere positioning, chromatin silencing, and lifespan. ..
  31. Xiao T, Shibata Y, Rao B, Laribee R, O Rourke R, Buck M, et al. The RNA polymerase II kinase Ctk1 regulates positioning of a 5' histone methylation boundary along genes. Mol Cell Biol. 2007;27:721-31 pubmed
  32. Larin M, Harding K, Williams E, Lianga N, Doré C, Pilon S, et al. Competition between Heterochromatic Loci Allows the Abundance of the Silencing Protein, Sir4, to Regulate de novo Assembly of Heterochromatin. PLoS Genet. 2015;11:e1005425 pubmed publisher
    ..Mutation of DOT1, the histone H3 lysine 79 (K79) methyltransferase, and SET1, the histone H3 lysine 4 (K4) methyltransferase, speed ..
  33. Stulemeijer I, De Vos D, van Harten K, Joshi O, Blomberg O, van Welsem T, et al. Dot1 histone methyltransferases share a distributive mechanism but have highly diverged catalytic properties. Sci Rep. 2015;5:9824 pubmed publisher
    The conserved histone methyltransferase Dot1 establishes an H3K79 methylation pattern consisting of mono-, di- and trimethylation states on histone H3 via a distributive mechanism...
  34. Lee S, Oh S, Jeong K, Jo H, Choi Y, Seo H, et al. Dot1 regulates nucleosome dynamics by its inherent histone chaperone activity in yeast. Nat Commun. 2018;9:240 pubmed publisher
    b>Dot1 (disruptor of telomeric silencing-1, DOT1L in humans) is the only known enzyme responsible for histone H3 lysine 79 methylation (H3K79me) and is evolutionarily conserved in most eukaryotes...
  35. Rossodivita A, Boudoures A, Mecoli J, Steenkiste E, Karl A, Vines E, et al. Histone H3 K79 methylation states play distinct roles in UV-induced sister chromatid exchange and cell cycle checkpoint arrest in Saccharomyces cerevisiae. Nucleic Acids Res. 2014;42:6286-99 pubmed publisher
  36. Granata M, Lazzaro F, Novarina D, Panigada D, Puddu F, Abreu C, et al. Dynamics of Rad9 chromatin binding and checkpoint function are mediated by its dimerization and are cell cycle-regulated by CDK1 activity. PLoS Genet. 2010;6: pubmed publisher
    ..CDK1-dependent phosphorylation of Rad9 on Ser11 leads to specific interaction with Dpb11, allowing Rad53 activation and bypassing the requirement for the histone branch. ..
  37. Hwang W, Madhani H. Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin. PLoS Genet. 2009;5:e1000588 pubmed publisher
    ..The nonredundant role for these modifications in this context contrasts with the notion of a highly combinatorial code by which histone marks act to control biological processes. ..
  38. Sampath V, Yuan P, Wang I, Prugar E, van Leeuwen F, Sternglanz R. Mutational analysis of the Sir3 BAH domain reveals multiple points of interaction with nucleosomes. Mol Cell Biol. 2009;29:2532-45 pubmed publisher
    ..These results, together with the previously characterized interaction between the C-terminal region of Sir3 and the histone H3/H4 tails, suggest that Sir3 utilizes multiple domains to interact with nucleosomes. ..
  39. Ng H, Dole S, Struhl K. The Rtf1 component of the Paf1 transcriptional elongation complex is required for ubiquitination of histone H2B. J Biol Chem. 2003;278:33625-8 pubmed
    ..b>Dot1, the H3-Lys79 methylase, associates with transcriptionally active genes, but unlike the association of Set1 and ..
  40. Bani Ismail M, Shinohara M, Shinohara A. Dot1-dependent histone H3K79 methylation promotes the formation of meiotic double-strand breaks in the absence of histone H3K4 methylation in budding yeast. PLoS ONE. 2014;9:e96648 pubmed publisher
    ..Set1 promotes H3K4 methylation while Dot1 promotes H3K79 methylation...
  41. Walter D, Matter A, Fahrenkrog B. Loss of histone H3 methylation at lysine 4 triggers apoptosis in Saccharomyces cerevisiae. PLoS Genet. 2014;10:e1004095 pubmed publisher
    ..In contrast, loss of H3K79 methylation due to DOT1 disruption only slightly affects yeast survival...
  42. Chen X, Cui D, Papusha A, Zhang X, Chu C, Tang J, et al. The Fun30 nucleosome remodeller promotes resection of DNA double-strand break ends. Nature. 2012;489:576-80 pubmed publisher
    ..Together these data suggest that Fun30 helps to overcome the inhibitory effect of Rad9 on DNA resection. ..
  43. Simoneau A, Ricard Ã, Weber S, Hammond Martel I, Wong L, Sellam A, et al. Chromosome-wide histone deacetylation by sirtuins prevents hyperactivation of DNA damage-induced signaling upon replicative stress. Nucleic Acids Res. 2016;44:2706-26 pubmed publisher
    ..Overall, our data support the concept that chromosome-wide histone deacetylation by sirtuins is critical to mitigate growth defects caused by endogenous genotoxins. ..
  44. Lee J, Shukla A, Schneider J, Swanson S, Washburn M, Florens L, et al. Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS. Cell. 2007;131:1084-96 pubmed
    ..H2B monoubiquitination by Rad6/Bre1 is required for both H3K4 methylation by COMPASS, and H3K79 methylation by Dot1. However, the molecular mechanism for such histone crosstalk is poorly understood...