皮肤癌是美国最常诊断的癌症类型，尽管大多数这类恶性肿瘤高度可治，治疗费用仍然每年超过80亿美元。在过去的50年中，皮肤癌的年发病率不断增加，因此，了解驱动这些癌症的环境因素是一个突出的研究重点。紫外线(UVR)照射与皮肤癌之间的因果关系已经得到确认，但仅仅接触到UVR并不一定足以诱导癌变。显微镜观察下，皮肤具有一个强大的昼夜节律，这对其对紫外线(UVR)照射的反应起到了一定的作用。本文将详细介绍昼夜节律的机制及其在细胞稳态中的作用。接下来，我们将介绍皮肤对紫外线(UVR)照射的反应、其引起的DNA损伤和突变，以及昼夜节律通过核苷酸切除修复影响其反应的重点。最后，本文还将讨论研究UVR引起的皮肤病变和昼夜节律紊乱的现有模型，以及这些因素对人类健康的影响。 版权©2022 Elsevier B.V.保留所有权利。

Skin cancer is the most diagnosed type of cancer in the United States, and while most of these malignancies are highly treatable, treatment costs still exceed $8 billion annually. Over the last 50 years, the annual incidence of skin cancer has steadily grown; therefore, understanding the environmental factors driving these types of cancer is a prominent research-focus. A causality between ultraviolet radiation (UVR) exposure and skin cancer is well-established, but exposure to UVR alone is not necessarily sufficient to induce carcinogenesis. The emerging field of circadian biology intersects strongly with the physiological systems of the mammalian body and introduces a unique opportunity for analyzing mechanisms of homeostatic disruption. The circadian clock refers to the approximate 24-hour cycle, in which protein levels of specific clock-controlled genes (CCGs) fluctuate based on the time of day. Though these CCGs are tissue specific, the skin has been observed to have a robust circadian clock that plays a role in its response to UVR exposure. This in-depth review will detail the mechanisms of the circadian clock and its role in cellular homeostasis. Next, the skin's response to UVR exposure and its induction of DNA damage and mutations will be covered - with an additional focus placed on how the circadian clock influences this response through nucleotide excision repair. Lastly, this review will discuss current models for studying UVR-induced skin lesions and perturbations of the circadian clock, as well as the impact of these factors on human health.Copyright © 2022 Elsevier B.V. All rights reserved.