DOT1-like (Disruptor of telomeric silencing 1-like), histone H3K79 methyltransferase (S. cerevisiae), also known as DOT1L, is a protein found in humans, as well as other eukaryotes.[5]
Quick Facts Available structures, PDB ...
DOT1L |
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Available structures |
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PDB | Human UniProt search: PDBe RCSB |
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List of PDB id codes |
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1NW3, 2MV7, 3QOW, 3QOX, 3SR4, 3SX0, 3UWP, 4EK9, 4EKG, 4EKI, 4EQZ, 4ER0, 4ER3, 4ER5, 4ER6, 4ER7, 4HRA, 4WVL, 5DSX, 5JUW, 5DRT, 5DTM, 5DTQ, 5DT2, 5DRY, 5DTR |
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Identifiers |
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Aliases | DOT1L, DOT1, KMT4, DOT1 like histone lysine methyltransferase |
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External IDs | OMIM: 607375; MGI: 2143886; HomoloGene: 32779; GeneCards: DOT1L; OMA:DOT1L - orthologs |
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Wikidata |
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DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias.[6] DOT1L also plays a role in spermatogenesis, where it acts as a transcriptional activator for genes responsible for the histone-to-protamine transition.[7]
Small molecule inhibitors of Dot1L catalytic activity have been developed.[8][9]
All three forms of H3K79 methylation (H3K79me1; H3K79me2; H3K79me3) are catalyzed by DOT1 in yeast or DOT1L in mammals. H3K79 methylation participates in the DNA damage response and has multiple roles in nucleotide excision repair and sister chromatid recombinational repair.[10]
Chen S, Li L, Chen Y, Hu J, Liu J, Liu YC, et al. (2016). "Identification of Novel Disruptor of Telomeric Silencing 1-like (DOT1L) Inhibitors through Structure-Based Virtual Screening and Biological Assays". Journal of Chemical Information and Modeling. 56 (3): 527–34. doi:10.1021/acs.jcim.5b00738. PMID 26914852.
- Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (April 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi:10.1093/dnares/8.2.85. PMID 11347906.
- Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, et al. (June 2002). "Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain". Current Biology. 12 (12): 1052–8. Bibcode:2002CBio...12.1052F. doi:10.1016/S0960-9822(02)00901-6. PMID 12123582. S2CID 17263035.
- Min J, Feng Q, Li Z, Zhang Y, Xu RM (March 2003). "Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase". Cell. 112 (5): 711–23. doi:10.1016/S0092-8674(03)00114-4. PMID 12628190. S2CID 17822742.
- Jikuya H, Takano J, Kikuno R, Hirosawa M, Nagase T, Nomura N, et al. (February 2003). "Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones". DNA Research. 10 (1): 49–57. doi:10.1093/dnares/10.1.49. PMID 12693554.
- Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, et al. (April 2005). "hDOT1L links histone methylation to leukemogenesis". Cell. 121 (2): 167–78. doi:10.1016/j.cell.2005.02.020. PMID 15851025. S2CID 15638573.
- Sistayanarain A, Tsuneyama K, Zheng H, Takahashi H, Nomoto K, Cheng C, et al. (2006). "Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma". Anticancer Research. 26 (5A): 3585–93. PMID 17094487.
- Overview of all the structural information available in the PDB for UniProt: Q8TEK3 (Histone-lysine N-methyltransferase, H3 lysine-79 specific) at the PDBe-KB.