Enhanced Nucleotide Excision Repair in Human Fibroblasts Pre-exposed to Ionizing Radiation

• Published in: Photochemistry and photobiology 2012-01, Vol.88 (1), p.147-153
• Main Authors: Cramers, Patricia, Filon, Alfred Ronald, Pines, Alex, Kleinjans, Jos C., Mullenders, Leon H. F., van Zeeland, Albert A.
• Format: Article
• Language: English
• Subjects: Base Sequence; Cell cycle; DNA damage; DNA Primers; DNA Repair; Fibroblasts - radiation effects; Humans; Oxidative stress; Photochemistry; Radiation, Ionizing; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/j.1751-1097.2011.01019.x

Cellular protection against deleterious effects of DNA damaging agents requires an intricate network of defense mechanisms known as the DNA damage response (DDR). Ionizing radiation (IR) mediated activation of the DDR induces a transcriptional upregulation of genes that are also involved in nucleotide excision repair (NER). This suggests that pre‐exposure to X‐rays might stimulate NER in human cells. Here, we demonstrate in normal human fibroblasts that UV‐induced NER is augmented by pre‐exposure to IR and that this increased repair is accompanied by elevated mRNA and protein levels of the NER factors XPC and DDB2. Furthermore, when IR exposure precedes local UV irradiation, the presence of XPC and DDB2 at the sites of local UV damages is increased. This increase might be p53 dependent, but the mechanism of X‐ray specific stabilization of p53 is unclear as both X‐rays and UV stabilize p53. Ionizing radiation mediated activation of the DNA damage response induces a transcriptional upregulation of genes that are also involved in nucleotide excision repair (NER). Here, we demonstrate in nondividing normal human fibroblasts that UV‐induced NER is augmented by pre‐exposure to IR. The increase of NER by IR lasts up to 48 h after X‐ray treatment. Furthermore, we show by various approaches that both DDB2 and XPC play key roles in this adaptation process.