DNA-3-methylguanine glycosylase activity
Definition
Target type: molecularfunction
Catalysis of the reaction: DNA containing 3-methylguanine + H2O = DNA with abasic site + 3-methylguanine. This reaction is the hydrolysis of DNA by cleavage of the N-C1' glycosidic bond between the damaged DNA 3-methylguanine and the deoxyribose sugar to remove the 3-methylguanine, leaving an abasic site. [EC:3.2.2.21, GOC:elh, PMID:10872450, PMID:9224623]
DNA-3-methylguanine glycosylase activity is a critical DNA repair mechanism that specifically removes 3-methylguanine (3MeG) from DNA. 3MeG is a mutagenic lesion caused by exposure to alkylating agents, such as methylating agents used in chemotherapy.
The enzyme responsible for this activity is called MGMT (O6-methylguanine-DNA methyltransferase). It functions as a DNA glycosylase, meaning it cleaves the glycosidic bond between 3MeG and the deoxyribose sugar backbone of DNA.
This single-step process removes the damaged base without the need for a DNA strand break. MGMT acts as a suicide enzyme, as it transfers the methyl group from 3MeG to a cysteine residue in its active site, becoming permanently inactivated in the process.
This irreversible inactivation ensures that the repair is complete and prevents the accumulation of 3MeG in DNA.
The activity of DNA-3-methylguanine glycosylase is essential for maintaining genomic stability and protecting cells from the detrimental effects of DNA damage caused by alkylating agents. It is a crucial component of the base excision repair (BER) pathway, which is responsible for removing a wide range of damaged bases from DNA.
The removal of 3MeG by MGMT is particularly important in cancer therapy, as it can prevent the accumulation of DNA damage that can lead to resistance to alkylating agents. In addition, MGMT activity is implicated in various biological processes, including aging and neurodegenerative diseases.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| DNA-3-methyladenine glycosylase | A DNA-3-methyladenine glycosylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P29372] | Homo sapiens (human) |
Compounds (4)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| aurintricarboxylic acid | aurintricarboxylic acid : A member of the class of quinomethanes that is 3-methylidene-6-oxocyclohexa-1,4-diene-1-carboxylic acid in which the methylidene hydrogens are replaced by 4-carboxy-3-hydroxyphenyl groups. The trisodium salt is the biological stain 'chrome violet CG' while the triammonium salt is 'aluminon'. Aurintricarboxylic Acid: A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues. | monohydroxybenzoic acid; quinomethanes; tricarboxylic acid | fluorochrome; histological dye; insulin-like growth factor receptor 1 antagonist |
| gossypol | Gossypol: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer. | ||
| mitoxantrone hydrochloride | hydrochloride | antineoplastic agent | |
| morin | morin : A pentahydroxyflavone that is 7-hydroxyflavonol bearing three additional hydroxy substituents at positions 2' 4' and 5. morin: a light yellowish pigment found in the wood of old fustic (Chlorophora tinctoria) | 7-hydroxyflavonol; pentahydroxyflavone | angiogenesis modulating agent; anti-inflammatory agent; antibacterial agent; antihypertensive agent; antineoplastic agent; antioxidant; EC 5.99.1.2 (DNA topoisomerase) inhibitor; hepatoprotective agent; metabolite; neuroprotective agent |