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Enhanced repair of cyclobutane pyrimidine dimers and improved UV resistance in photolyase transgenic mice
Author(s) -
Schul Wouter,
Jans Judith,
Rijksen Yvonne M.A.,
Klemann Kyra H.M.,
Eker Andre P.M.,
de Wit Jan,
Nikaido Osamu,
Nakajima Satoshi,
Yasui Akira,
Hoeijmakers Jan H.J.,
van der Horst Gijsbertus T.J.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf456
Subject(s) - photolyase , pyrimidine dimer , biology , nucleotide excision repair , dna repair , microbiology and biotechnology , dna damage , transgene , dna , genetics , gene
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 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.