4.6 Article

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

期刊

JOURNAL OF DERMATOLOGICAL SCIENCE
卷 105, 期 3, 页码 152-158

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2022.01.009

关键词

Xeroderma pigmentosum; UV irradiation; Microarray; Replication-related gene; Mitotic gene

资金

  1. Japan Agency for Medical Research and Development (AMED) [JP15ek0109028h0002]
  2. Ministry of Health, Labour and welfare (MHLW) , Japan [20FC1043]

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This study aimed to analyze the differential gene expression in XP-A cells after UV irradiation. The results showed that the number of genes with significantly altered expression in XP-A cells at 12 hours was higher compared to normal cells, indicating a correlation between the number of altered genes and DNA damage. The study found that the XPA protein can transcriptionally inhibit replication-related genes and regulate DNA replication and re-replication after UV irradiation.
Background: 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.Objective: We aimed to ascertain the genes differentially regulated in XP complementation group A (XP-A) cells after UV irradiation. Methods: 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.Results: 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.Conclusion: 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.(c) 2022 Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.

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