Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes.
Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced.
Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, Québec City, Québec, Canada.|Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Université Laval, Québec City, Québec, Canada.|Département d'Ophtalmologie et ORL-chirurgie cervico-faciale, Université Laval, Québec City, Québec, Canada.
Justin D
JD
Mallet
Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, Québec City, Québec, Canada.|Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Université Laval, Québec City, Québec, Canada.|Département d'Ophtalmologie et ORL-chirurgie cervico-faciale, Université Laval, Québec City, Québec, Canada.
Marie M
MM
Dorr
Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, Québec City, Québec, Canada.|Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Université Laval, Québec City, Québec, Canada.|Département d'Ophtalmologie et ORL-chirurgie cervico-faciale, Université Laval, Québec City, Québec, Canada.
Marie-Catherine
MC
Drigeard Desgarnier
Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, Québec City, Québec, Canada.|Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Université Laval, Québec City, Québec, Canada.|Département d'Ophtalmologie et ORL-chirurgie cervico-faciale, Université Laval, Québec City, Québec, Canada.
Nathalie
N
Bastien
Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, Québec City, Québec, Canada.|Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Université Laval, Québec City, Québec, Canada.|Département d'Ophtalmologie et ORL-chirurgie cervico-faciale, Université Laval, Québec City, Québec, Canada.
Sébastien P
SP
Gendron
Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, Québec City, Québec, Canada.|Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Université Laval, Québec City, Québec, Canada.|Département d'Ophtalmologie et ORL-chirurgie cervico-faciale, Université Laval, Québec City, Québec, Canada.
Patrick J
PJ
Rochette
D017209:Apoptosis / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D019573:Epithelium, Corneal / Q000166:cytology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D011740:Pyrimidine Dimers / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D011740:Pyrimidine Dimers; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C086984:XPC protein, human