Powerful skin cancer protection by a CPD-photolyase transgene

Curr Biol. 2005 Jan 26;15(2):105-15. doi: 10.1016/j.cub.2005.01.001.


Background: The high and steadily increasing incidence of ultraviolet-B (UV-B)-induced skin cancer is a problem recognized worldwide. UV introduces different types of damage into the DNA, notably cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts (6-4PPs). If unrepaired, these photolesions can give rise to cell death, mutation induction, and onset of carcinogenic events, but the relative contribution of CPDs and 6-4PPs to these biological consequences of UV exposure is hardly known. Because placental mammals have undergone an evolutionary loss of photolyases, repair enzymes that directly split CPDs and 6-4PPs into the respective monomers in a light-dependent and lesion-specific manner, they can only repair UV-induced DNA damage by the elaborate nucleotide excision repair pathway.

Results: To assess the relative contribution of CPDs and 6-4PPs to the detrimental effects of UV light, we generated transgenic mice that ubiquitously express CPD-photolyase, 6-4PP-photolyase, or both, thereby allowing rapid light-dependent repair of CPDs and/or 6-4PPs in the skin. We show that the vast majority of (semi)acute responses in the UV-exposed skin (i.e., sunburn, apoptosis, hyperplasia, and mutation induction) can be ascribed to CPDs. Moreover, CPD-photolyase mice, in contrast to 6-4PP-photolyase mice, exhibit superior resistance to sunlight-induced tumorigenesis.

Conclusions: Our data unequivocally identify CPDs as the principal cause of nonmelanoma skin cancer and provide genetic evidence that CPD-photolyase enzymes can be employed as effective tools to combat skin cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Carcinoma / etiology*
  • Carcinoma / prevention & control
  • Cell Line
  • DNA Damage / radiation effects*
  • DNA Repair / genetics*
  • Deoxyribodipyrimidine Photo-Lyase / genetics
  • Deoxyribodipyrimidine Photo-Lyase / metabolism*
  • Gene Expression
  • Mice
  • Mice, Transgenic
  • Pyrimidine Dimers / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / prevention & control
  • Ultraviolet Rays*


  • Pyrimidine Dimers
  • pyrimidine-pyrimidone dimer
  • Deoxyribodipyrimidine Photo-Lyase