Impact of the Circadian Clock on UV-Induced DNA Damage Response and Photocarcinogenesis.
Impact of the Circadian Clock on UV-Induced DNA Damage Response and Photocarcinogenesis.
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DOI：
10.1111/php.12662
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发表时间：
2017-01
影响因子：
3.3
通讯作者：
Gaddameedhi S
中科院分区：
文献类型：
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作者：
Dakup P;Gaddameedhi S
皮肤持续暴露于各种外部环境应激源，包括太阳紫外线（UV）辐射。各种波长的紫外线被皮肤中的DNA和其他分子吸收，导致DNA损伤和诱导氧化应激。暴露于过量的紫外线（UV）辐射和/或损伤随时间的累积可导致光致癌和光老化。核苷酸切除修复（NER）系统是从DNA中去除UV光产物损伤的唯一机制，该修复途径的遗传破坏导致光敏性疾病着色性干皮病（XP）。有趣的是，最近的研究表明，NER是由生物钟控制的，生物钟是人体的自然时间保持机制，通过调节限速修复因子着色性干皮病A组（XPA）。研究表明，与早晨相比，晚上暴露于紫外线后，紫外线诱导的皮肤癌减少，这分别对应于高和低修复能力的时间。然而，大多数关于昼夜节律钟-NER连接的研究都使用了小鼠模型，因此将这些发现转化为人类以改善皮肤癌预防和时间疗法是很重要的。皮肤暴露在阳光下会导致DNA损伤。因此，身体通过各种防御机制对这种环境损伤做出反应，包括核苷酸切除修复，这是由生物钟调节的。因此，一天中的时间对于确定紫外线辐射对皮肤的致突变和致癌潜力非常重要。
The skin is in constant exposure to various external environmental stressors, including solar ultraviolet (UV) radiation. Various wavelengths of UV light are absorbed by the DNA and other molecules in the skin to cause DNA damage and induce oxidative stress. The exposure to excessive ultraviolet (UV) radiation and/or accumulation of damage over time can lead to photocarcinogenesis and photoaging. The nucleotide excision repair (NER) system is the sole mechanism for removing UV photoproduct damage from DNA, and genetic disruption of this repair pathway leads to the photosensitive disorder xeroderma pigmentosum (XP). Interestingly, recent work has shown that NER is controlled by the circadian clock, the body’s natural time keeping mechanism, through regulation of the rate-limiting repair factor xeroderma pigmentosum group A (XPA). Studies have shown reduced UV-induced skin cancer after UV exposure in the evening compared to the morning, which corresponds with times of high and low repair capacities, respectively. However, most studies of the circadian clock-NER connection have utilized murine models, and it is therefore important to translate these findings to humans to improve skin cancer prevention and chronotherapy. Exposure of the skin to sunlight causes DNA damage. As a result, the body responds to this environmental insult through various defensive mechanisms including the nucleotide excision repair, which is regulated by the circadian clock. Hence, the time-of-the-day is important in determining the mutagenic and carcinogenic potential of UVR insult to the skin.