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

The locus frequently appears as an abnormal, fragile-site-like structure rather than a clean replicated pair. A1, B3 and C2 have one dominant signal instead of a clearly resolved sister pair; A2/A4, B1/B4 and C1/C3 show extra, split or irregularly distributed signal components. These patterns are compatible with incomplete replication, abnormal condensation of sister chromatids, or splitting and fragmentation of the repeat-containing region. A single signal can also result from unresolved sisters or inefficient hybridization, so it is not automatically a deletion.

The several small signals should not simply be counted as newly created intact copies: stretching, gaps and fragmentation can divide the fluorescent image of an existing locus. Conversely, amplification would require independent copy-number evidence. The fact that aberrant structures occur in non-infected biological cells indicates intrinsic vulnerability of this host region, rather than a requirement for NVNA1 in their initial appearance. These images alone do not distinguish an undercondensed but continuous DNA region from a genuine DNA double-strand break. Their sensitivity to replication inhibition provides the next mechanistic clue.