CPDs and 6-4PPs play different roles in UV-induced cell death in normal and NER-deficient human cells.
Ultraviolet (UV) light generates two major DNA lesions: cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs), but the specific participation of these two lesions in the deleterious effects of UV is a longstanding question. In order to discriminate the precise role of unrepaired CPDs and 6-4PPs in UV-induced responses triggering cell death, human fibroblasts were transduced by recombinant adenoviruses carrying the CPD-photolyase or 6-4PP-photolyase cDNAs. Both photolyases were able to prevent UV-induced apoptosis in cells deficient for nucleotide excision repair (NER) to a similar extent, while in NER-proficient cells UV-induced apoptosis was prevented only by CPD-photolyase, with no effects observed when 6-4PPs were removed by the specific photolyase. These results strongly suggest that both CPDs and 6-4PPs contribute to UV-induced apoptosis in NER-deficient cells, while in NER-proficient cells, CPDs are the only lesions responsible for UV-killing, probably due to the rapid repair of 6-4PPs by NER. As a consequence, the difference in skin photosensitivity, including carcinogenesis, of most of the xeroderma pigmentosum patients and of normal people is probably not only a quantitative aspect, but depends on the type of DNA damage induced by sunlight and its rate of repair.
de Lima-Bessa
Keronninn Moreno
KM
Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, Avenue Prof Lineu Prestes, São Paulo, SP, Brazil.
Armelini
Melissa Gava
MG
Chiganças
Vanessa
V
Jacysyn
Jacqueline F
JF
Amarante-Mendes
Gustavo P
GP
Sarasin
Alain
A
Menck
Carlos Frederico Martins
CF
D000256:Adenoviridae; D016923:Cell Death / Q000528:radiation effects*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000528:radiation effects*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011740:Pyrimidine Dimers / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics; D014161:Transduction, Genetic; D014466:Ultraviolet Rays
D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011740:Pyrimidine Dimers; D018160:Receptors, Cytoplasmic and Nuclear; C058406:pyrimidine-pyrimidone dimer