Disease relevance of ECs3102

• Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase [1].
• Cloning and characterization of the Salmonella typhimurium ada gene, which encodes O6-methylguanine-DNA methyltransferase [2].
• A constitutive O6-methylguanine-DNA methyltransferase of Rhizobium meliloti [3].
• The ada+ gene of E. coli is a regulatory gene of the adaptive response to simple alkylating agents. ada mutants are sensitive to both the mutagenicity and toxicity of alkylating agents, and are unable to induce O6-methylguanine DNA methyltransferase and 3-methyladenine DNA glycosylase II [4].

High impact information on ECs3102

• Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA methyltransferase from E. coli [5].
• The O6-methylguanine-DNA methyltransferase of Escherichia coli acts rapidly and stoichiometrically to convert a mutagenic O6-methylguanine residue in DNA to unsubstituted guanine [1].
• Amino acid sequence determinations show that the active center for the O6-methylguanine-DNA methyltransferase is located close to the polypeptide COOH terminus and has the unusual sequence -Pro-Cys-His-, preceded by a very hydrophobic region [6].
• The repair of O6-methylguanine present in N-methylnitrosourea (MNU)-treated alternating polynucleotides MNU-poly(dG-dC) X poly(dG-dC) and MNU-poly(dG-me5dC) X poly(dG-me5dC] was investigated using O6-methylguanine-DNA methyltransferase purified from Escherichia coli [7].
• An O6-methylguanine-DNA methyltransferase has been partially purified from calf thymus by conventional biochemical techniques [8].

Chemical compound and disease context of ECs3102

• The E. coli ada gene encodes O6-methylguanine DNA methyltransferase (O6MTase) which repairs the methylation of guanine at the O6 position in DNA [9].

Biological context of ECs3102

• The nucleotide sequence contained two open reading frames that were assigned to the genes adaA and adaB, encoding methylphosphotriester-DNA methyltransferase and O6-methylguanine-DNA methyltransferase, respectively [10].
• This enhancement of mutagenesis by SOS was unaffected by prior treatment of the DNA with O6-methylguanine DNA methyltransferase [11].
• When the same methylated plasmid was repaired in vitro by using purified O6-methylguanine DNA methyltransferase (to correct O6-methylguanine and O4-methylthymine), no mutations were detected above background levels [11].
• It is therefore suggested that the mechanism of induction of the adaptive response may involve direct methylation of the O6-methylguanine-DNA methyltransferase itself [12].

Associations of ECs3102 with chemical compounds

• Cross-linking of DNA induced by chloroethylnitrosourea is presented by O6-methylguanine-DNA methyltransferase [13].
• In partially repair-proficient cells, the Ada O6-methylguanine-DNA methyltransferase repair protein was twice as efficient on m6G when a guanine base rather than an adenine base was 5' to the lesion [14].
• Neither mutant protein had O6-methylguanine-DNA methyltransferase activity, but both retained the phosphotriester-DNA methyltransferase activity involving methyl group transfer to Cys-69 [15].
• At least two enzymes are induced during the response: 3-methyladenine DNA glycosylase II and O6-methylguanine DNA methyltransferase [16].
• The present study revealed that potent comutagenic activity of o-vanillin in mutagenesis by N-methyl-N-nitrosourea (MNU) is a consequence of inhibition of the transcriptional promoting capacity of methylated O6-methylguanine-DNA methyltransferase (MGTase) [17].

Analytical, diagnostic and therapeutic context of ECs3102

• Crystallization of O6-methylguanine-DNA methyltransferase from Escherichia coli [18].

References