N7-methyl G (7meG)

FULL NAME: N7-methylguanine


DESCRIPTION:
The N7 atom of guanine (G) is the most chemically vulnerable site to attack by alkylating electrophiles as it has the highest negative electrostatic potential of all the other atoms within the DNA bases. This property also makes it a highly reactive ligand for metal ions such as platinum. When double-stranded DNA is treated with MMS or MNNG, 82 and 67% of the methylation occurs on the N7 position of guanine, respectively. Within the cell, 7meG is produced at the rate of 4000 residues/human genome/day by the non-enzymatic reaction of SAM with DNA, and its steady-state level in repair-proficient cells is estimated to be 3000 bases. 7meG has been detected in human DNA at the level of a few adducts per 10v7 bases. 7MeG by itself does not have any major mutagenic or cytotoxic effects. However, methylation at the N7 position destabilizes the N-glycosidic bond leading to spontaneous depurination of this lesion and the resulting AP sites are toxic. AP sites can also be formed during repair of 7meG by N-alkylpurine DNA-glycosylases, which are part of the BER pathway. Although not examined directly in the context of alkylation, the mutagenic and toxic properties of AP sites have been thoroughly investigated. In addition to its role as a source of AP sites, 7MeG can manifest toxicity by converting to its imidazole ring-opened form. Hydrolysis of the imidazole ring of 7meG forms 2,6-diamino-4-hydroxy-5N-methyl-formamidopyrimidine (Fapy-7meG). 7meG by itself is not toxic to cells. 7meG is recognized and excised by lesion-specific DNA glycosylases, namely AlkA, Fpg (MutM), Tag in E. coli and ANPG (MPG) in humans. SID 24885085 CID 11361 CHEBI:28664 CHEBI:2274 KEGG COMPOUND C02242 CAS 578-76-7 InChI 1S/C6H7N5O/c1-11-2-8-4-3(11)5(12)10-6(7)9-4/h2H,1H3,(H3,7,9,10,12) InChIKey FZWGECJQACGGTI-UHFFFAOYSA-N

DAMAGE TYPE: methylation damage


DNA DAMAGE SOURCE(S) (MAIN):
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
SN1 methylating agents
SN2 methylating agents
methyl methanesulfonate (MMS)
alkylating agents


DNA DAMAGE SOURCE(S) (MINOR):
streptozotocin


DNA DAMAGE EFFECT(S) (MAIN):
no mutagenesis


DNA DAMAGE EFFECT(S) (MINOR):
AP-site
mutagenesis
point mutation
substitution


PATHWAYS:
base excision repair (BER)


DNA repair protein(s) related to damage:
AlkA
Fpg (MutM)
Tag
ANPG (MPG)


Last modification date: Sept. 21, 2011