Target type: molecularfunction
Catalysis of the reaction: DNA with alkylated base + H2O = DNA with abasic site + alkylated base. This reaction is the hydrolysis of DNA by cleavage of the N-C1' glycosidic bond between the target damaged DNA base and the deoxyribose sugar to remove an alkylated base, leaving an apyrimidinic or apurinic site. [EC:3.2.2.21, GOC:elh, PMID:10872450, PMID:9224623]
Alkylbase DNA N-glycosylase activity is a critical component of DNA repair mechanisms, specifically targeting the removal of alkylated bases from DNA. Alkylation, a process where alkyl groups (e.g., methyl, ethyl) are attached to DNA bases, can distort the DNA structure and disrupt its normal function. This can lead to mutations, impaired gene expression, and even cell death.
Alkylbase DNA N-glycosylases function by recognizing and excising the alkylated base from the DNA backbone, leaving an apurinic/apyrimidinic (AP) site. This process involves the following steps:
1. **Recognition**: The enzyme identifies the alkylated base through specific interactions with its modified structure. Different alkylbase DNA N-glycosylases exhibit varying substrate specificities, targeting different alkylated bases (e.g., methylguanine, ethylthymine).
2. **Cleavage**: The enzyme cleaves the N-glycosidic bond between the alkylated base and the deoxyribose sugar in the DNA backbone. This leaves the base detached and an AP site behind.
3. **Base removal**: The enzyme releases the alkylated base, which is then further degraded in the cell.
4. **AP site processing**: The AP site is processed by other enzymes, including AP endonucleases, which remove the damaged sugar-phosphate backbone. This generates a gap in the DNA that can then be filled in by DNA polymerase and ligase, restoring the original DNA sequence.
Alkylbase DNA N-glycosylase activity is essential for maintaining genomic integrity and preventing the accumulation of mutations caused by alkylating agents. These agents can be naturally occurring or introduced through environmental exposures (e.g., smoking, industrial chemicals). The repair process mediated by alkylbase DNA N-glycosylases helps protect cells from the damaging effects of alkylation and ensures the accurate transmission of genetic information.'
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| 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) |
| 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 |