7-methyl A (7meA)

FULL NAME: 7-methyladenine


DESCRIPTION:
N7-methyladenine (7MeA) is a minor lesion formed at a level 40-fold below that of 7MeG, which is typically the most abundant lesion in alkylated DNA. Like 7MeG, 7MeA possesses a cationic imidazole ring, which facilitates depurination and, alternatively, can favor hydrolysis of the five-membered ring to form the formamidopyrimidine (Fapy) derivative, Fapy-7MeA; this latter hydrolysis reaction is especially favored for the 7MeA in RNA, which has a stabilized glycosidic bond as compared with DNA. The half-life of 7MeA in DNA in vivo is only 2–3 hours, which is similar to its half-life in vitro at pH 7.2, 37°C. Fapy-7MeA is a mutagenic lesion displaying A → G transitions in single-stranded M13mp18 DNA transfected into SOS-induced E.coli. In these studies, dimethylsulfate-treated DNA was compared before and after treatment with alkali, which hydrolyzed the imidazole rings of N7-methylated adenines and guanines, forming the Fapy derivatives. Dimethylsulfate- and alkali-treated DNA was 60-fold more mutagenic than DNA treated with dimethylsulfate alone and showed mutations primarily at A:T sites. REACTION: an alkylated DNA = a DNA containing a purinic site + 7-methylguanine + 3-methyladenine + 7-methyladenine + 3-methylguanine, a purine ribonucleoside + phosphate = a purine base + α-D-ribose-1-phosphate

DAMAGE TYPE: methylation damage


DNA DAMAGE SOURCE(S) (MAIN):
SN2 methylating agents
methyl methanesulfonate (MMS)
alkylating agents


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


PATHWAYS:
base excision repair (BER)


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


Last modification date: Nov. 9, 2011