Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, Montevideo 11600, Uruguay.
Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay.
Environ Toxicol Pharmacol. 2022 Nov;96:104001. doi: 10.1016/j.etap.2022.104001. Epub 2022 Oct 20.
Exposure to ultraviolet radiation from sunlight induces oxidative DNA lesions and bipyrimidine photoproducts that can lead to photo-aging and skin carcinogenesis. CPD-photolyases are flavoproteins that repair cyclobutane pyrimidine dimers using blue light as an energy source. In the present work, we evaluated the photo-repair effect of the recombinant CPD-photolyase PhrAHym from the Antarctic bacterium Hymenobacter sp. UV11 on DNA lesions in human keratinocytes induced by UVC light. By performing immunochemistry assays we observed that PhrAHym repairs in a highly efficient way the CPD-photoproducts and reduces the γH2AX formation. Since this enzyme is non-cytotoxic and repairs UVC-induced DNA lesions in human keratinocytes, we propose that PhrAHym could be used as a biotherapeutic agent against UV-induced skin cancer, photoaging, and related diseases.
阳光中的紫外线辐射会诱发氧化 DNA 损伤和嘧啶二聚体光产物,从而导致皮肤光老化和皮肤癌发生。CPD 光解酶是一类黄素蛋白,它们利用蓝光作为能量来源修复环丁烷嘧啶二聚体。在本工作中,我们评估了来自南极细菌 Hymenobacter sp. UV11 的重组 CPD 光解酶 PhrAHym 对 UVC 光诱导的人角质形成细胞 DNA 损伤的光修复作用。通过进行免疫化学分析,我们观察到 PhrAHym 能够高效修复 CPD 光产物,并减少 γH2AX 的形成。由于该酶无细胞毒性且能修复 UVC 诱导的人角质形成细胞中的 DNA 损伤,因此我们提出 PhrAHym 可用作针对 UV 诱导的皮肤癌、光老化和相关疾病的生物治疗剂。