Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Japan.
Atomic Energy Research Institute, Kindai University.
J Dermatol Sci. 2022 Mar;105(3):152-158. doi: 10.1016/j.jdermsci.2022.01.009. Epub 2022 Feb 4.
Xeroderma pigmentosum (XP) is hereditary disorder characterized by photosensitivity, predisposition to skin cancers of sun-exposed body sites and progressive neurologic symptoms in some cases. Cells from XP patients show higher sensitivity to ultraviolet radiation (UV) than normal cells.
We aimed to ascertain the genes differentially regulated in XP complementation group A (XP-A) cells after UV irradiation.
XP-A cells were harvested at 4 or 12 h after a single exposure to low-dose UV-C radiation and subjected to transcriptome analysis by microarray.
The number of genes with significantly altered expression (≥2-fold difference) at 12 h was markedly higher in XP-A cells than that in normal cells, suggesting that the number of altered genes could be correlated to the amount of DNA damage.
We recently reported that mitotic genes are induced in normal human fibroblasts after UV-C exposure, and similar results were observed in XP-A cells as normal cells. In addition, a majority of replication-related genes were significantly upregulated in XP-A cells, whereas no such expression pattern was observed in the normal control cells. Collectively, these results indicate that the XPA protein can transcriptionally inhibit the series of replication-related genes, and could possibly regulate replication and/or re-replication after UV irradiation.
着色性干皮病（XP）是一种遗传性疾病，其特征为对阳光敏感、易患暴露于阳光的身体部位的皮肤癌以及在某些情况下出现进行性神经症状。与正常细胞相比，XP 患者的细胞对紫外线（UV）辐射的敏感性更高。
我们旨在确定 XP 互补组 A（XP-A）细胞在 UV 照射后差异调节的基因。
XP-A 细胞在单次低剂量 UV-C 辐射后 4 或 12 小时收获，并通过微阵列进行转录组分析。
在 XP-A 细胞中，12 小时时表达明显改变（≥2 倍差异）的基因数量明显高于正常细胞，这表明改变的基因数量可能与 DNA 损伤的量有关。
我们最近报道，UV-C 暴露后正常人类成纤维细胞中诱导有丝分裂基因，在 XP-A 细胞中也观察到与正常细胞相似的结果。此外，大多数与复制相关的基因在 XP-A 细胞中显著上调，而在正常对照细胞中则没有观察到这种表达模式。总之，这些结果表明 XPA 蛋白可以转录抑制一系列与复制相关的基因，并且可能在 UV 照射后调节复制和/或再复制。
