Q.11 Which type of enzyme in known to remove methyl or ethyl groups from Guanine
bases that have been mutagenized by Alkylating agents?
(1)Photolyase
(2) DNA N-glycosylases
(3) Alkyltransferase
(4) AP endonuclease
Alkyltransferase removes methyl or ethyl groups from mutagenized Guanine bases. This enzyme, specifically O6-alkylguanine-DNA alkyltransferase (AGT or MGMT), directly transfers the alkyl group from O6-guanine to a cysteine residue in its active site, repairing the damage in a single step without breaking the DNA backbone.
Option Analysis
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(1) Photolyase: Repairs UV-induced cyclobutane pyrimidine dimers by splitting bonds using photolyase’s flavin cofactor and blue light; ineffective against alkylation.
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(2) DNA N-glycosylases: Initiate base excision repair (BER) by cleaving N-glycosidic bonds of damaged purines/pyrimidines (e.g., 3-methyladenine), creating AP sites; do not handle O6-guanine alkylation.
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(3) Alkyltransferase: Correct—AGT/MGMT stoichiometrically transfers methyl/ethyl from O6-guanine (and O4-thymine) to Cys145, self-inactivating after one repair event.
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(4) AP endonuclease: Acts downstream in BER, incising the DNA backbone at apurinic/apyrimidinic (AP) sites after glycosylase removal; does not remove alkyl groups.
The answer is (3) Alkyltransferase.
Introduction to Alkyltransferase DNA Repair
Alkylating agents like MNNG create cytotoxic O6-methylguanine (O6-meG), pairing with thymine and causing G-to-A mutations. The enzyme that removes methyl or ethyl groups from Guanine bases is alkyltransferase (O6-alkylguanine-DNA alkyltransferase, AGT), providing direct reversal repair.
Mechanism of Direct Reversal
AGT’s active cysteine (Cys145 in humans) performs SN2 nucleophilic attack on the alkyl group, transferring it irreversibly and restoring guanine. One AGT molecule repairs one lesion, then degrades—suicide enzyme mechanism.
Other Repair Enzymes Differentiated
Photolyase fixes UV dimers via photoreactivation; N-glycosylases excise N-alkyl bases in BER; AP endonuclease processes abasic sites post-glycosylase. Only alkyltransferase targets O6-alkylation.
GATE Life Sciences Relevance
Critical for molecular biology: Distinguish direct reversal (alkyltransferase) from excision pathways. MGMT silencing links to cancer chemotherapy resistance.
