Replication-related genes are upregulated in XP-A cells after UV-C irradiation

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.