Adaptive amplification of ERG11 copies has been documented as a recurrent mechanism of azole resistance, often arising through unequal sister chromatid exchange within subtelomeric zones (Flowers et al., 2015; Finkel et al., 2021). Such amplification events are facilitated by the replication stress inherent to telomeric proximity, where replication fork collapse promotes break-induced replication cycles. The result is a dynamic mosaic of ERG11 copy numbers across populations, generating dosage variation that buffers against drug inhibition. This process exemplifies nuclear-level evolutionary design: structural fragility is repurposed as an adaptive mechanism, yielding a continuum between genomic instability and phenotypic robustness.

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