Dnmt2 is the most evolutionary conserved and enigmatic cytosine DNA methyltransferase in eukaryotes
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  • 作者:V. V. Ashapkin ; L. I. Kutueva ; B. F. Vanyushin
  • 关键词:DNA methylation ; 5 ; methylcytosine ; DNA methyltransferase ; Dnmt2 ; tRNA methylation ; evolution
  • 刊名:Russian Journal of Genetics
  • 出版年:2016
  • 出版时间:March 2016
  • 年:2016
  • 卷:52
  • 期:3
  • 页码:237-248
  • 全文大小:396 KB
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  • 作者单位:V. V. Ashapkin (1)
    L. I. Kutueva (1)
    B. F. Vanyushin (1)

    1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Biomedicine
    Human Genetics
    Animal Genetics and Genomics
    Microbial Genetics and Genomics
    Russian Library of Science
  • 出版者:MAIK Nauka/Interperiodica distributed exclusively by Springer Science+Business Media LLC.
  • ISSN:1608-3369
文摘
Dnmt2 is the most strongly conserved cytosine DNA methyltransferase in eukaryotes. It has been found in all organisms possessing methyltransferases of the Dnmt1 and Dnmt3 families, whereas in many others Dnmt2 is the sole cytosine DNA methyltransferase. The Dnmt2 molecule contains all conserved motifs of cytosine DNA methyltransferases. It forms 3D complexes with DNA very similar to those of bacterial DNA methyltransferases and performs cytosine methylation by a catalytic mechanism common to all cytosine DNA methyltransferases. Catalytic activity of the purified Dnmt2 with DNA substrates is very low and could hardly be detected in direct biochemical assays. Dnmt2 is the sole cytosine DNA methyltransferase in Drosophila and other dipteran insects. Its overexpression as a transgene leads to DNA hypermethylation in all sequence contexts and to an extended life span. On the contrary, a null-mutation of the Dnmt2 gene leads to a diminished life span, though no evident anomalies in development are observed. Dnmt2 is also the sole cytosine DNA methyltransferase in several protists. Similar to Drosophila these protists have a very low level of DNA methylation. Some limited genome compartments, such as transposable sequences, are probably the methylation targets in these organisms. Dnmt2 does not participate in genome methylation in mammals, but seems to be an RNA methyltransferase modifying the 38th cytosine residue in anticodon loop of certain tRNAs. This modification enhances stability of tRNAs, especially in stressful conditions. Dnmt2 is the only enzyme known to perform RNA methylation by a catalytic mechanism characteristic of DNA methyltransferases. The Dnmt2 activity has been shown in mice to be necessary for paramutation establishment, though the precise mechanisms of its participation in this form of epigenetic heredity are unknown. It seems likely, that either of the two Dnmt2 activities could become a predominant one during the evolution of different species. The high level of the Dnmt2 evolutionary conservation proves its activity to have a significant adaptive value in natural environment.

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