A cancer cell develops resistance to methotrexate through amplification of the DHFR gene. Which process of DNA replication is most analogous to gene amplification in terms of mechanism?

• A Telomere elongation
• B Strand slippage during replication of tandem repeats
• C Homologous recombination between sister chromatids ✓
• D Nucleotide excision repair followed by re-synthesis

Explanation

Gene amplification typically arises through unequal crossing over during homologous recombination between sister chromatids or homologous chromosomes, generating one chromatid with a deletion and another with a tandem duplication. Repeated rounds of unequal recombination can expand copy number dramatically. The resulting extra DHFR gene copies produce excess dihydrofolate reductase protein, overwhelming the inhibitory concentration of methotrexate and restoring thymidylate synthesis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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