Nakanishi Makoto, Niida Hiroyuki, Murakami Hiroshi, Shimada Midori
Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
J Dermatol Sci. 2009 Nov;56(2):76-81. doi: 10.1016/j.jdermsci.2009.09.001. Epub 2009 Sep 24.
UV irradiation is the main etiological cause of most types of skin cancers and can accelerate skin photoaging. UV irradiation results in several types of DNA damage in eukaryotic cells, such as DNA single strand breaks, DNA interstrand cross-links, and nucleotide base modifications. In response to such DNA damages, mammalian cells exert DNA damage responses including cell cycle checkpoints, well-developed DNA repair, apoptosis and premature senescence to prevent genomic instability. Cell cycle checkpoints are important surveillance systems to maintain genomic integrity. Once checkpoint systems sense the abnormal chromosomal DNA structures, they execute cell cycle arrest through inhibiting the activity of cell cycle regulators and coordinate it with the DNA repair process. Checkpoint responses also execute cellular senescence when cells sense unrepairable and extensive chromosomal abnormalities. Senescent cells are no longer able to divide despite remaining viable for long periods of time, metabolically active, but functionally impaired. Accumulation of senescent cells in skin results in harmful consequences such as skin aging. Therefore, skin photoaging is thought to be a phenotypic hallmark responsible for one of the major mechanisms against skin carcinogenesis. In this review, changes in chromatin modification in response to UV and the molecular mechanisms accelerating aging phenotypes are discussed.
紫外线照射是大多数类型皮肤癌的主要病因，并且会加速皮肤光老化。紫外线照射会导致真核细胞中出现几种类型的DNA损伤，如DNA单链断裂、DNA链间交联和核苷酸碱基修饰。针对此类DNA损伤，哺乳动物细胞会产生DNA损伤反应，包括细胞周期检查点、完善的DNA修复、细胞凋亡和早衰，以防止基因组不稳定。细胞周期检查点是维持基因组完整性的重要监测系统。一旦检查点系统检测到异常的染色体DNA结构，它们会通过抑制细胞周期调节因子的活性来执行细胞周期阻滞，并将其与DNA修复过程协调起来。当细胞检测到无法修复的广泛染色体异常时，检查点反应也会导致细胞衰老。衰老细胞尽管能够长时间存活且代谢活跃，但功能受损，不再能够分裂。皮肤中衰老细胞的积累会导致诸如皮肤老化等有害后果。因此，皮肤光老化被认为是对抗皮肤癌发生的主要机制之一的表型标志。在这篇综述中，我们讨论了紫外线照射后染色质修饰的变化以及加速衰老表型的分子机制。
