N6-methyladenine: the other methylated base of DNA - PubMed (original) (raw)

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N6-methyladenine: the other methylated base of DNA

David Ratel et al. Bioessays. 2006 Mar.

Abstract

Contrary to mammalian DNA, which is thought to contain only 5-methylcytosine (m5C), bacterial DNA contains two additional methylated bases, namely N6-methyladenine (m6A), and N4-methylcytosine (m4C). However, if the main function of m5C and m4C in bacteria is protection against restriction enzymes, the roles of m6A are multiple and include, for example, the regulation of virulence and the control of many bacterial DNA functions such as the replication, repair, expression and transposition of DNA. Interestingly, even if adenine methylation is usually considered a bacterial DNA feature, the presence of m6A has been found in protist and plant DNAs. Furthermore, indirect evidence suggests the presence of m6A in mammal DNA, raising the possibility that this base has remained undetected due to the low sensitivity of the analytical methods used. This highlights the importance of considering m6A as the sixth element of DNA.

Copyright 2006 Wiley Periodicals, Inc.

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Figures

Fig. 1

Fig. 1

Schematic representation of the phylogenetic distribution of m6A in DNA.

Fig. 2

Fig. 2. Some established and putative functions of m6A in DNA

A) Restriction-modifications systems defend bacteria from invasions by viral DNA. These systems are composed of a bacterial restriction enzyme which cuts a specific sequence in phage DNA, and a cognate adenine or cytosine DNA methyltransferase which recognizes the same target site that the restriction enzyme and protects bacterial DNA from its own restriction enzyme(s). B) In E. coli, adenine methylation is also used to discriminate the transiently unmethylated newly synthesized complementary strand during DNA replication. This discrimination is the basis of the methyl-directed mismatch repair which makes correction on the newly synthesized strand only. C) Alteration in the levels of DNA adenine methylation attenuates the virulence of a number of pathogens. D) Speculative representation of the biological functions of putative eucaryotic N-6 adenine-specific DNA methylase(s).

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