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Sci Rep ; 9(1): 2753, 2019 02 26.
Article in English | MEDLINE | ID: mdl-30808882

ABSTRACT

Ultraviolet light induced pyrimidine dimer is a helix distortion DNA damage type, which recruits repair complexes. However, proteins of these complexes that take part in both DNA damage recognition and repair have been well-described, the regulation of the downstream steps of nucleotide excision repair (NER) have not been clearly clarified yet. In a high-throughput screen, we identified SerpinB2 (SPB2) as one of the most dramatically upregulated gene in keratinocytes following UV irradiation. We found that both the mRNA and the protein levels of SPB2 were increased upon UV irradiation in various cell lines. Additionally, UV damage induced translocation of SPB2 from the cytoplasm to the nucleus as well as the damage induced foci formation of it. Here we show that SPB2 co-localizes with XPB involved in the NER pathway at UV-induced repair foci. Finally, we demonstrated that UV irradiation promoted the association of SPB2 with ubiquitylated proteins. In basal cell carcinoma tumour cells, we identified changes in the subcellular localization of SPB2. Based on our results, we conclude that SPB2 protein has a novel role in UV-induced NER pathway, since it regulates the removal of the repair complex from the damaged site leading to cancerous malformation.


Subject(s)
DNA Damage , DNA Repair , Melanoma/pathology , Osteosarcoma/pathology , Plasminogen Activator Inhibitor 2/metabolism , Ultraviolet Rays/adverse effects , Bone Neoplasms/etiology , Bone Neoplasms/pathology , Carcinoma, Basal Cell/etiology , Carcinoma, Basal Cell/pathology , DNA Helicases/genetics , DNA Helicases/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Melanoma/etiology , Osteosarcoma/etiology , Plasminogen Activator Inhibitor 2/genetics , Pyrimidine Dimers , Tumor Cells, Cultured
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