6-O-Methylguanine
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| Names | |
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| IUPAC name
6-Methoxy-7H-purin-2-amine
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| Other names
6-Methoxyguanine; O6-Methylguanine; 2-Amino-6-methoxypurine
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| Identifiers | |
20535-83-5  |
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| ChEMBL | ChEMBL226395  |
| ChemSpider | 58766 |
| Jmol 3D model | Interactive image Interactive image |
| PubChem | 65275 |
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| Properties | |
| C6H7N5O | |
| Molar mass | 165.16 g·mol−1 |
| Melting point | >300 °C |
| Vapor pressure | {{{value}}} |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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| Infobox references | |
6-O-Methylguanine is a derivative of the nucleobase guanine in which a methyl group is attached to the oxygen atom. It base-pairs to thymine rather than cytidine, causing a G:C to A:T transition in DNA.
Contents
Formation
6-O-methylguanine is formed in DNA by alkylation of the oxygen atom of guanine, most often by N-nitroso compounds (NOC)[2] and sometimes due to methylation by other compounds such as endogenous S-adenosyl methionine.[3] NOC are alkylating agents formed by the reaction of nitrite or other nitrogen oxides with secondary amines and N-alkylamides, yielding N-alkylnitrosamines and N-alkylnitrosamides.[2]
NOC are found in some foods (bacon, sausages, cheese) and tobacco smoke, and are formed in the gastrointestinal tract, especially after consumption of red meat.[2] In addition, endogenous nitric oxide levels were found to be enhanced under chronic inflammatory conditions, and this could favor NOC formation in the large intestine.
Repair and carcinogenicity
Repair of 6-O-methylguanine in DNA is primarily carried out by O-6-methylguanine-DNA methyltransferase (MGMT). Epigenetic reductions in MGMT expression are one of the most frequent DNA repair defects, associated with carcinogenesis.[4] (Also see MGMT expression in cancer.)
Mutagenicity
In 1985 Yarosh summarized the early work that established 6-O-methylguanine as the alkylated base in DNA that was the most mutagenic and carcinogenic.[5] In 1994 Rasouli-Nia et al.[6] showed that about one mutation was induced for every eight unrepaired 6-O-Methylguanines in DNA.
About 1/3rd of the time 6-O-methylguanine mispairs during replication, leading to the incorporation of dTMP rather than dCMP.[7] 6-O-methylguanine is therefore a mutagenic nucleobase. However, the mutagenicity of a particular 6-O-methylguanine base depends on the sequence in which it is embedded.[8]
Other effects
Unrepaired 6-O-methylguanine can also lead to cell cycle arrest, sister chromatid exchange, or apoptosis.[9] These effects are due to interaction of the DNA mismatch repair pathway with 6-O-methylguanine, and also depend on signaling network activation, led by early ATM, H2AX, CHK1 and p53 phosphorylation.[9]
See also
References
- ↑ 6-O-Methylguanine at Sigma-Aldrich
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