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.
Highlights
Our genome is constantly exposed to endogenous and exogenous sources leading to DNA damage and impairment of genome integrity
We demonstrated that UV irradiation resulted in increased SPB2 mRNA and protein levels in various cell types
U2OS cells showed similar but weaker increase in the mRNA level of SPB2. This could be explained by evolutionary conserved mechanisms in response to UV irradiation, which is more emphasised in keratinocyte cells, since those are normally exposed to UV light
Summary
Our genome is constantly exposed to endogenous and exogenous sources leading to DNA damage and impairment of genome integrity. The serine protease inhibitor superfamily, called Serpins, consists of highly heterogenic proteins taking part in tumorigenesis, blood clotting, hormone transport, inflammation, immune function and mucous production[7]. It has been reported that protein members of the SerpinB clade regulate processes related to inflammation, immune system function, mucous production, apoptosis, tumour metastasis www.nature.com/scientificreports/. We have found differences in the subcellular localization of SPB2 between normal and tumorous parts of the examined human basal cell carcinoma tissues. These results further support our hypothesis that SPB2 could function as a repair protein in normal cells since the translocation of the protein to the nucleus is blocked in tumorous cells thereby interfering with its DNA repair function
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