Past exam of the biochemistry course of the University of Cambridge / 2024 / Paper 5 / Section 1 / m

aphidicolin increases the abnormal-locus fraction from roughly 40% to about 55–60% in all three lines. Inhibition of replicative DNA polymerases increases replication stress at an intrinsically difficult-to-complete region. Tandem repeats can complicate fork progression or chromosome organization. Slower or incomplete synthesis leaves underreplicated DNA, unresolved replication intermediates or abnormal condensation as biological cells approach mitosis; these can appear as split signals or gaps and can predispose to actual breakage.

This is an increase of approximately 15–20 percentage points, not proof of a 15–20-fold change. The two independent measurements per condition support a reproducible direction, but the graph does not provide enough information for a precise significance calculation or a quantitative model of fork failure. aphidicolin need not bind NVNA1 or the repeat sequence directly. Because these are uninfected biological cells, the result establishes susceptibility of the host locus to replication stress independently of viral protein expression.