Which of the following would most likely cause cell death?

• A. Small base lesions
• B. Single-strand breaks
• C. Double-strand breaks
• D. Double-strand breaks and single-strand breaks will always lead to permanent damage

Answer: (C)

Double-strand breaks are the most lethal type of DNA damage because both strands of the DNA double helix are broken. Repairing them correctly is challenging and requires rejoining the ends without losing information. If the ends are misrepaired or if the breaks overwhelm the repair machinery, chromosomes can fragment, rearrange, or lose essential genes, leading to loss of cell function and activation of cell-death pathways.

In contrast, small base lesions are usually fixed by base-excision repair, and single-strand breaks are repaired by dedicated single-strand repair mechanisms. Even if not repaired immediately, these lesions are generally less likely to cause immediate cell death because the unbroken strand can serve as a template for accurate restoration and replication can proceed after repair. The idea that all double-strand breaks and single-strand breaks always result in permanent damage isn’t accurate, since cells can and do repair many such lesions; however, double-strand breaks pose the greatest threat to survival.