Detection of the small oligonucleotide products of nucleotide excision repair in UVB-irradiated human skin.,DNA Repair

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Detection of the small oligonucleotide products of nucleotide excision repair in UVB-irradiated human skin.
DNA Repair ( IF 3.0 ) Pub Date : 2019-12-05 , DOI: 10.1016/j.dnarep.2019.102766
Jun-Hyuk Choi ₁ , Sueji Han ₁ , Michael G Kemp ₂

Affiliation

UVB radiation results in the formation of potentially mutagenic photoproducts in the DNA of epidermal skin cells. In vitro approaches have demonstrated that the nucleotide excision repair (NER) machinery removes UV photoproducts from DNA in the form of small (∼30-nt-long), excised, damage-containing DNA oligonucleotides (sedDNAs). Though this process presumably takes place in human skin exposed to UVB radiation, sedDNAs have not previously been detected in human skin. Using surgically discarded human skin, we have optimized the detection of the sedDNA products of NER from small amounts of human epidermal tissue ex vivo within minutes of UVB exposure and after UVB doses that normally lead to minimal erythema. Moreover, sedDNA generation was inhibited by treatment of skin explants with spironolactone, which depletes the epidermis of the essential NER protein XPB to mimic the skin of xeroderma pigmentosum patients. Time course experiments revealed that a partially degraded form of the sedDNAs could be readily detected even 12 hours following UVB exposure, which indicates that these repair products are relatively stable in human skin epidermis. Together, these data suggest that sedDNA detection may be a useful assay for determining how genetic, environmental, and other factors influence NER activity in human skin epidermis and whether abnormal sedDNA processing contributes to photosensitive skin disorders.

中文翻译：

在紫外线照射的人体皮肤中进行核苷酸切除修复的小寡核苷酸产物的检测。

UVB辐射导致在表皮皮肤细胞的DNA中形成潜在的诱变光产物。体外方法已证明，核苷酸切除修复（NER）机器可以从DNA中去除紫外线光产物，形式为小的（〜30 nt长），切离的，含有损伤的DNA寡核苷酸（sedDNA）。尽管此过程可能发生在暴露于UVB辐射的人体皮肤中，但以前尚未在人体皮肤中检测到sedDNA。使用外科丢弃的人皮肤，我们优化了从少量人表皮组织离体的NER的sedDNA产物的检测，方法是在UVB暴露的几分钟内和通常导致最小的红斑的UVB剂量后离体。此外，通过使用螺内酯处理皮肤外植体可抑制sedDNA的产生，它消耗了必需的NER蛋白XPB的表皮，以模仿色干性皮肤病患者的皮肤。时程实验表明，即使在暴露于UVB后12小时，sedDNA的部分降解形式也很容易被检测到，这表明这些修复产品在人的皮肤表皮中相对稳定。总之，这些数据表明，sedDNA检测可能是确定遗传，环境和其他因素如何影响人皮肤表皮中NER活性以及异常sedDNA处理是否导致光敏性皮肤疾病的有用测定方法。这表明这些修复产品在人的皮肤表皮中相对稳定。总之，这些数据表明，sedDNA检测可能是确定遗传，环境和其他因素如何影响人皮肤表皮中NER活性以及异常sedDNA处理是否导致光敏性皮肤疾病的有用测定方法。这表明这些修复产品在人的皮肤表皮中相对稳定。总之，这些数据表明，sedDNA检测可能是确定遗传，环境和其他因素如何影响人皮肤表皮中NER活性以及异常sedDNA处理是否导致光敏性皮肤疾病的有用测定方法。

更新日期：2019-12-05

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