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词条 DOT1L
释义

  1. References

  2. Further reading

{{Infobox_gene}}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][2]

The methylation of histone H3 lysine 79 (H3K79) by DOT1L which is a conserved epigenetic mark in many eukaryotic epigenomes, increases progressively along the aging process, suggesting that "DOT1L might function as a vital clock, ticking the hours impassively".[3]

DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias[4]

Small molecule inhibitors of Dot1L catalytic activity have been developed.[5][6]

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.[7]

References

1. ^{{cite web | title = Entrez Gene: DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84444| accessdate = }}
2. ^{{cite journal | vauthors = Vlaming H, van Leeuwen F | year = 2016 | title = The upstreams and downstreams of H3K79 methylation by DOT1L | url = | journal = Chromosoma | volume = 125| issue = | pages = 1–13 | doi = 10.1007/s00412-015-0570-5 }}
3. ^{{cite journal | vauthors = Soria-Valles C, Osorio FG, López-Otín C | year = 2015 | title = Reprogramming aging through DOT1L inhibition | url = | journal = Cell Cycle | volume = 14 | issue = 21| pages = 3345–3346 | doi = 10.1080/15384101.2015.1093443 | pmc = 4825545 }}
4. ^{{cite journal | vauthors = Slany RK | title = The molecular mechanics of mixed lineage leukemia | journal = Oncogene | volume = | issue = | pages = | year = 2016 | pmid = 26923329 | doi = 10.1038/onc.2016.30 }}
5. ^{{cite journal | vauthors = Yao Y, Chen P, Diao J, Cheng G, Deng L, Anglin JL, Prasad BV, Song Y | title = Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies | journal = Journal of the American Chemical Society | volume = 133 | issue = 42 | pages = 16746–9 | year = 2011 | pmid = 21936531 | pmc = 3492951 | doi = 10.1021/ja206312b }}
6. ^{{cite journal | vauthors = Chen S, Li L, Chen Y, Hu J, Liu J, Liu YC, Liu R, Zhang Y, Meng F, Zhu K, Lu J, Zheng M, Chen K, Zhang J, Jiang H, Yao Z, Luo C | title = Identification of Novel Disruptor of Telomeric Silencing 1-like (DOT1L) Inhibitors through Structure-Based Virtual Screening and Biological Assays | journal = Journal of Chemical Information and Modeling | volume = 56 | issue = 3 | pages = 527–34 | year = 2016 | pmid = 26914852 | doi = 10.1021/acs.jcim.5b00738 }}
7. ^{{cite journal |vauthors=Chen Y, Zhu WG |title=Biological function and regulation of histone and non-histone lysine methylation in response to DNA damage |journal=Acta Biochim. Biophys. Sin. (Shanghai) |volume=48 |issue=7 |pages=603–16 |date=July 2016 |pmid=27217472 |doi=10.1093/abbs/gmw050 |url=}}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O | title = 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 | journal = DNA Research | volume = 8 | issue = 2 | pages = 85–95 | date = April 2001 | pmid = 11347906 | doi = 10.1093/dnares/8.2.85 }}
  • {{cite journal | vauthors = Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y | title = Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain | journal = Current Biology | volume = 12 | issue = 12 | pages = 1052–8 | date = June 2002 | pmid = 12123582 | doi = 10.1016/S0960-9822(02)00901-6 }}
  • {{cite journal | vauthors = Min J, Feng Q, Li Z, Zhang Y, Xu RM | title = Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase | journal = Cell | volume = 112 | issue = 5 | pages = 711–23 | date = March 2003 | pmid = 12628190 | doi = 10.1016/S0092-8674(03)00114-4 }}
  • {{cite journal | vauthors = Jikuya H, Takano J, Kikuno R, Hirosawa M, Nagase T, Nomura N, Ohara O | title = Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones | journal = DNA Research | volume = 10 | issue = 1 | pages = 49–57 | date = February 2003 | pmid = 12693554 | doi = 10.1093/dnares/10.1.49 }}
  • {{cite journal | vauthors = Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, Su L, Xu G, Zhang Y | title = hDOT1L links histone methylation to leukemogenesis | journal = Cell | volume = 121 | issue = 2 | pages = 167–78 | date = April 2005 | pmid = 15851025 | doi = 10.1016/j.cell.2005.02.020 }}
  • {{cite journal | vauthors = Sistayanarain A, Tsuneyama K, Zheng H, Takahashi H, Nomoto K, Cheng C, Murai Y, Tanaka A, Takano Y | title = Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma | journal = Anticancer Research | volume = 26 | issue = 5A | pages = 3585–93 | year = 2006 | pmid = 17094487 | doi = }}
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