DNA as the critical target

  • Direct effect: Ionization of DNA molecules themselves.

  • Indirect effect: Ionization of water → formation of reactive oxygen species (ROS) such as hydroxyl radicals → DNA damage.

Types of damage

  • Single-strand break (SSB): One strand of the DNA helix is broken; usually repaired accurately.

  • Double-strand break (DSB): Both strands break near each other; highly lethal if unrepaired, mutagenic if misrepaired.

  • Base damage: Alteration or loss of DNA bases.

Repair pathways

  • Non-homologous end joining (NHEJ): Quick repair by directly rejoining broken ends, but error-prone. Active in all cell cycle phases.

  • Homologous recombination (HR): Accurate repair using a sister chromatid as a template; only active in late S and G2 phases.

  • Base excision repair (BER): Fixes small, non-helix-distorting lesions (oxidized bases, SSBs).

Definitions

  • Free radicals: Atoms or molecules with unpaired electrons, highly reactive.

  • ROS (Reactive oxygen species): Oxygen-based free radicals (like hydroxyl radical, superoxide).

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