O6-methyl G (O6meG)

FULL NAME: O6-methylguanine


DESCRIPTION:
O6-methylguanine (O6meG), which causes G → A transitions, is the primary mutagenic lesion under most conditions of alkylation damage to the genome. O6MeG is formed from both endogenous and exogenous sources. O6MeG is known to be highly mutagenic. It was found that the predominant mutation generated by this lesion was a G → A transition. O6MeG can inhibit carbon-5 methylation of cytosines in 5′-deoxycytidine-deoxyguanosine-3′ (dCpG) motifs by interfering with the binding of 5-methylcytosine DNA methyltransferases; eventually, this interference with natural methylation can lead to genome hypomethylation. The pairing of O6MeG with thymine can also lead to DNA hypomethylation. By these mechanisms, the formation of this adduct could affect the epigenetic program of mammalian cells.

DAMAGE TYPE: methylation damage


DNA DAMAGE SOURCE(S) (MAIN):
SN1 methylating agents
alkylating agents


DNA DAMAGE EFFECT(S) (MAIN):
G→A transition
mutagenesis
point mutation
substitution
transition


PATHWAYS:
direct reversal (DR)


DNA repair protein(s) related to damage:
Ada
Ogt
MGMT


Last modification date: Oct. 12, 2011