Biology:DOT1L
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.[1]
DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias.[2] DOT1L also plays a role in spermatogenesis, where it acts as a transcriptional activator for genes responsible for the histone-to-protamine transition.[3]
Small molecule inhibitors of Dot1L catalytic activity have been developed.[4][5]
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.[6]
References
- ↑ "Entrez Gene: DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae)". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=84444.
- ↑ "The molecular mechanics of mixed lineage leukemia". Oncogene 35 (40): 5215–5223. October 2016. doi:10.1038/onc.2016.30. PMID 26923329.
- ↑ "DOT1L promotes spermatid differentiation by regulating expression of genes required for histone-to-protamine replacement". Development 150 (9). May 2023. doi:10.1242/dev.201497. PMID 37082969.
- ↑ "Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies". Journal of the American Chemical Society 133 (42): 16746–9. 2011. doi:10.1021/ja206312b. PMID 21936531. Bibcode: 2011JAChS.13316746Y.
- ↑ "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. 2016. doi:10.1021/acs.jcim.5b00738. PMID 26914852.
- ↑ "Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage". Acta Biochim. Biophys. Sin. (Shanghai) 48 (7): 603–16. July 2016. doi:10.1093/abbs/gmw050. PMID 27217472.
Further reading
- "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. April 2001. doi:10.1093/dnares/8.2.85. PMID 11347906.
- "Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain". Current Biology 12 (12): 1052–8. June 2002. doi:10.1016/S0960-9822(02)00901-6. PMID 12123582. Bibcode: 2002CBio...12.1052F. https://cdr.lib.unc.edu/downloads/5425kk607.
- "Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase". Cell 112 (5): 711–23. March 2003. doi:10.1016/S0092-8674(03)00114-4. PMID 12628190.
- "Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones". DNA Research 10 (1): 49–57. February 2003. doi:10.1093/dnares/10.1.49. PMID 12693554.
- "hDOT1L links histone methylation to leukemogenesis". Cell 121 (2): 167–78. April 2005. doi:10.1016/j.cell.2005.02.020. PMID 15851025.
- "Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma". Anticancer Research 26 (5A): 3585–93. 2006. PMID 17094487.
External links
- 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.
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