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

Wouter Schul, Judith Jans, Yvonne M.A. Rijksen, Kyra H.M. Klemann, Andre P.M. Eker, Jan De Wit, Osamu Nikaido, Satoshi Nakajima, Akira Yasui, Jan H.J. Hoeijmakers, Gijsbertus T.J. Van der Horst

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    69 Citations (Scopus)

    Abstract

    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 β-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 photoreactivate 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.

    Original languageEnglish
    Pages (from-to)4719-4729
    Number of pages11
    JournalEMBO Journal
    Volume21
    Issue number17
    DOIs
    Publication statusPublished - 2002 Sep 2

    Keywords

    • Cyclobutane pyrimidine dimers
    • Photolyase transgenic mice
    • Photoreactivation
    • UV sensitivity

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)

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  • Cite this

    Schul, W., Jans, J., Rijksen, Y. M. A., Klemann, K. H. M., Eker, A. P. M., De Wit, J., Nikaido, O., Nakajima, S., Yasui, A., Hoeijmakers, J. H. J., & Van der Horst, G. T. J. (2002). Enhanced repair of cyclobutane pyrimidine dimers and improved UV resistance in photolyase transgenic mice. EMBO Journal, 21(17), 4719-4729. https://doi.org/10.1093/emboj/cdf456