Which type of DNA damage is most likely to cause cell death?

The type of DNA damage most likely to cause cell death is double-strand breaks. This is because double-strand breaks create a more severe disruption in the DNA structure compared to other forms of damage. When both strands of the DNA helix are broken, it can lead to extensive loss of genetic material and can compromise essential cellular functions.

Cells have mechanisms to repair single-strand breaks; these often do not have fatal consequences because the complementary strand remains intact, allowing for accurate repair. Base substitutions and point mutations are relatively minor alterations that can frequently be corrected by cellular repair systems and, if not correctly repaired, may lead to mutations but often do not result in immediate cell death.

In contrast, double-strand breaks can be particularly catastrophic, as they may not only lead to cell cycle arrest and apoptosis (programmed cell death) if the damage is too great to repair, but they can also result in genomic instability, leading to potential cancer development. Therefore, due to the severity and potential consequences of double-strand breaks, they are the most critical type of DNA damage in the context of cell viability.