UV-Mediated NF-κB Activation is Abolished in Deficient XPC/D Primary Fibroblasts

Genetic pathologies involving deficits in DNA repair, like xeroderma pigmentosum (XP), show recurrent cell death, tissue degeneration and oncogenesis due to high sensitivity to ultraviolet radiation (UV). Various inducers including UV activate NF-κB, a pathway largely involved in cell proliferation and apoptosis. However, the mechanism(s) involving NF-κB activation by UV are poorly understood. To improve this knowledge, we examined NF-κB in two XP cell groups (XPC and XPD/TTD). XPC/D primary fibroblasts possess functional NF-κB dimers, and pro-inflammatory cytokines consistently activate NF-κB pathway. Contrarily, UV-mediated NF-κB activation is practically absent, whereas κB-specific DNA binding and transcriptional activity are dramatically undermined. These results indicate that lack of UV responsiveness at the NF-κB level is a common feature of XPC/D cells, suggesting that XP proteins might act upstream on NF-κB activity induced by UV. These observations help us to better understand the UV sensitivity and compromised survival of XP deficient cells.

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