R5.4a: Types Of DNA Lesions

DNA damage occurs due to the ionisation of molecules as they interact with radiation. The direct effect of radiation is due to the primary radiation beam interacting with the target molecule, in this case DNA. The indirect effect relies on the secondary radiation generated by the primary radiation to deposit the damage. The ratio of direct to indirect effect varies with different radiation qualities. Alpha particles have a large direct effect whereas photons are more reliant on the generation of secondary electrons and radical ions.
The damage caused by ionising radiation includes:

  • Damage to bases, repaired through base excision repair. Some base damage is repaired through nucleotide excision repair.
  • Single strand breaks, repaired through single strand break repair
  • Double strand breaks, repaired through homologous recombination or non-homologous end joining

Other mechanisms of DNA Damage

DNA damage due to other mechanisms may also occur, but mutations in the genes which code for their repair proteins does not influence sensitivity to ionising radiation. Common sources of damage include:

  • Normal metabolic processes
    • Free radical generation during metabolism
    • DNA replication may be associated with transcription errors, repaired through a number of pathways
  • External sources
    • Non-ionising radiation, such as UV electromagnetic radiation, can cause crosslinks between adjacent bases
    • Chemicals may react with DNA, causing adducts (additions to the DNA molecule that disrupt its structure) or crosslinks
    • Heat can cause breakage of DNA molecules

Base mismatch, which often occurs during DNA replication, is repaired with mismatch repair proteins (MMR). Bulky DNA lesions or adducts are repaired by nucleotide excision repair (NER). Other processes to remove specific adducts are also present.

Each Gy of radiation leads to about 100,000 ionisations within a cell, damage to over 1,000 bases, about 1,000 single strand DNA breaks and about 20 – 40 double strand breaks. Despite this, 1 Gy kills only 30% of mammalian cells due to the effectiveness of DNA repair - particularly for non-DSB lesions.