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  • The EMBO Journal (2002) 21, 4719 - 4729
  • doi:10.1093/emboj/cdf456

Enhanced repair of cyclobutane pyrimidine dimers and improved UV resistance in photolyase transgenic mice

Wouter Schul1,4, Judith Jans1,4, Yvonne M.A. Rijksen1, Kyra H.M. Klemann1, Andre P.M. Eker1, Jan de Wit1, Osamu Nikaido2, Satoshi Nakajima3, Akira Yasui3, Jan H.J. Hoeijmakers1 and Gijsbertus T.J. van der Horst1

  1. MGC, Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands
  2. Division of Radiation Biology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
  3. Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
  4. W.Schul and J.Jans contributed equally to this work

Correspondence to:

Gijsbertus T.J. van der Horst, E-mail: vanderhorst@gen.fgg.eur.nl

Received 18 February 2002; Accepted 15 July 2002; Revised 15 July 2002

During evolution, placental mammals appear to have lost cyclobutane pyrimidine dimer (CPD) photolyase, an enzyme that efficiently removes UV-induced CPDs from DNA in a light-dependent manner. As a consequence, they have to rely solely on the more complex, and for this lesion less efficient, nucleotide excision repair pathway. To assess the contribution of poor repair of CPDs to various biological effects of UV, we generated mice expressing a marsupial CPD photolyase transgene. Expression from the ubiquitous beta-actin promoter allowed rapid repair of CPDs in epidermis and dermis. UV-exposed cultured dermal fibroblasts from these mice displayed superior survival when treated with photoreactivating light. Moreover, photoreactivation of CPDs in intact skin dramatically reduced acute UV effects like erythema (sunburn), hyperplasia and apoptosis. Mice expressing the photolyase from keratin 14 promoter photo reactivate CPDs in basal and early differentiating keratinocytes only. Strikingly, in these animals, the anti-apoptotic effect appears to extend to other skin compartments, suggesting the presence of intercellular apoptotic signals. Thus, providing mice with CPD photolyase significantly improves repair and uncovers the biological effects of CPD lesions.

  • Keywords:

    • cyclobutane pyrimidine dimers,
    • photolyase transgenic mice,
    • photoreactivation,
    • UV sensitivity