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4. DNA LESIONS

KINDS OF DAMAGE, INCLUDING OXIDATION

  • Single strand breaks
  • Double strand breaks
  • Small base changes (oxidation and alkylation)
  • Bulky adducts
  • DNA crosslinks (intrastrand and interstrand)

SMALL BASE CHANGES (oxidation and alkylation)

Repaired by base excision repair (BER) - see animation later.

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/small_base_changes.jpg

BULKY ADDUCTS

E.g. heterocyclic amines, benzoapyrene, aflatoxin

Repaired by nucleotide excision repair (NER)

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/bulky-adducts.jpg

DNA CROSSLINKS

  • Intrastrand crosslinks (distorting the helix)

Repaired by nucleotide excision repair (NER)

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/cyclobutane_pyrimidine_dimer.jpg

  • Interstrand crosslinks

Psoralens intercalate in the DNA and, with the help of UV A light, covalently bind to pyrimidines in one or both strands. The cross-linking effectively arrests replication.
Psoralens + light are used to treat psoriasis (excessive proliferation of epithelial cells in skin).
Unfortunately, psoralens are also mutagenic. A side-effect of long-time exposure is enhanced cancer risk.

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-biology/illustrations/psoralen-crosslink.jpg