Disease relevance of N6-Methyladenine

• Similar analysis of E. coli B methylation products indicated that the bulk of methyl groups incorporated into the base moieties of tRNA (1- and 7-methylguanine, 2- and N6-methyladenine, and 5-methyluracil) occurred prior to the formation of 2'-0-methylribose derivatives [1].
• Expression of Escherichia coli dam gene in Bacillus subtilis provokes DNA damage response: N6-methyladenine is removed by two repair pathways [2].
• (ii) the N6-methyladenine content of phage L DNA was measured after growth in various host strains; phage lacking SA modification contained fewer N6-methyladenine residues per DNA [3].
• Methyl-specific restriction appears to be common in Streptomyces spp., since either N6-methyladenine-specific or 5-methylcytosine-specific restriction was observed in seven of nine strains tested [4].
• Restriction analysis of plasmid pHV14 deoxyribonucleic acid isolated from Escherichia coli K-12, Bacillus subtilis, and staphylococcus aureus with restriction endonucleases MboI, Sau3AI, and EcoRII was used to study the methylation of those nucleotide sequences which in E. coli contain the major portions of N6-methyladenine and 5-methylcytosine [5].

High impact information on N6-Methyladenine

• The extrachromosomal rRNA genes (rDNA) of Tetrahymena thermophila contain 0.4% N6-methyladenine [6].
• DNA in the polyploid macronucleus of the ciliated protozoan Tetrahymena thermophila contains the modified base N6-methyladenine [7].
• In the product of EcoRI enzymatic methylation, all of the isotope remains at the N6 position of the N6-methyladenine product [8].
• We propose that N6-methyladenine residues are excised by proteins involved in both excision (uvrB) and the adaptive response (ada) DNA repair pathways in B. subtilis [2].
• Formation of internal N6-methyladenine (m6A) residues in the DHFR transcript was shown to increase slightly by the absence of a 7-methylguanine-2'-O-methyl cap structure [9].

Chemical compound and disease context of N6-Methyladenine

• Postreplicative methylation of adenine in Escherichia coli DNA to produce G6m ATC (where 6mA is 6-methyladenine) has been associated with preferential daughter-strand repair and possibly regulation of replication [10].

Biological context of N6-Methyladenine

• DNA methylation in thermophilic bacteria: N4-methylcytosine, 5-methylcytosine, and N6-methyladenine [11].
• Previous X-ray crystallographic studies have revealed that the catalytic domain of a DNA methyltransferase (Mtase) generating C5-methylcytosine bears a striking structural similarity to that of a Mtase generating N6-methyladenine [12].
• The enzyme does not liberate several other alkylation products from DNA, including 7-methylguanine,O6-methylguanine, 7-methyladenine, N6-methyladenine, 7-ethylguanine, O6-ethylguanine, and the arylalkylated purine derivatives obtained by treatment of DNA with 7-bromomethyl-12-methylbenz[a]anthracene [13].
• The transformation frequency was reduced greater than 1,000-fold when plasmid DNA was modified by dam or TaqI methylases to contain N6-methyladenine or by AluI, HhaI, HphI methylases to contain 5-methylcytosine [4].
• In its cis isomer, N6-methyladenine destabilizes hydrogen bonding by interfering with pseudo-Watson-Crick base pairing [14].

Anatomical context of N6-Methyladenine

• Practically no complement fixation has been found with DNAs containing no N6-methyladenine, such as calf thymus, salmon sperm, Micrococcus radiodurans, Streptomyces chrysomallus and Streptomyces hygroscopicus, whereas a weak reactivity occurred in the case of Bacillus subtilis DNA and Sarcina maxima DNA [15].

Associations of N6-Methyladenine with other chemical compounds

• The methylase recognizes the symmetric tetranucleotide d(pG-A-T-C) and introduces two methyl groups per site in duplex DNA with the product of methylation being 6-methylaminopurine [16].
• Neither 6-methylaminopurine arabinoside nor 6-dimethylaminopurine arabinoside was detectably phosphorylated by either adenosine kinase or 2'-deoxycytidine kinase [17].
• Surprisingly, the purified R.MmeI endonuclease was found to have a second enzymatic activity, namely methylation of the adenine residue to N6-methyladenine in the top strand of the MmeI-recognition sequence, 5'-TCCR*AC-3' (*A=meA [18].
• Influence of local duplex stability and N6-methyladenine on uracil recognition by mismatch-specific uracil-DNA glycosylase (Mug) [14].

Gene context of N6-Methyladenine

• We suggest that mrr encodes an endonuclease that cleaves DNA containing N6-methyladenine and that DNA double-strand breaks induce the SOS response [19].
• In Escherichia coli polA lig-4 bacteria, the moles percent 6-methyladenine content of 10S deoxyribonucleic acid (Okazaki fragments) is 0.96 compared with 1.4 for bulk desoxyribonucleic acid [20].
• Using nonadecameric duplex deoxyoligonucleotide substrates, the specificity of the PaeR7 endonuclease for unmethylated, hemi-methylated, and fully methylated N6-methyladenine (m6A) and C5-methylcytosine (m5C) versions of these substrates has been studied [21].
• A mutant of BamHI restriction endonuclease which requires N6-methyladenine for cleavage [22].
• Two forms of a 6-methyladenine mRNA methyltransferase have been partially purified using a T7 transcript coding for mouse dihydrofolate reductase as an RNA substrate [23].

Analytical, diagnostic and therapeutic context of N6-Methyladenine

• The product of methylation was identified by paper chromatography as N6-methyladenine [24].
• The enzyme recognizes the palindromic sequence 5'-G(met-A,A)TC-3' as determined by PEI chromatography of pancreatic DNase, snake venom phosphodiesterase digestion products of labelled fragments, analysis of restriction digests from normal and N6-methyladenine-free DNA and direct sequence analysis of cloned fragments [25].
• Determination of 6-methyladenine in DNA by high-performance liquid chromatography [26].
• A method for the determination of 6-methyladenine (6MA) by high-performance liquid chromatography (HPLC) has been developed [26].

References