Aldehyde-mediated protein degradation is responsible for the inhibition of nucleotide excision repair by cigarette sidestream smoke

CSS strongly inhibited the repair of UVB-induced DNA damage, pyrimidine(6-4)pyrimidone photoproducts (6-4PPs), where the recruitments of repair molecules, TFIIH and XPG, were slowed down. F-CSS showed similar inhibition of NER and accumulation of related proteins, but the effect was weaker than CSS. Semicarbazide (SEM), an aldehyde-trapping agent, alleviated the NER delay induced by both CSS and F-CSS, further confirming that aldehydes in CSS were the main cause for the inhibition of NER and that the different amounts of aldehydes in CSS and F-CSS were responsible for the different inhibition efficiency. Furthermore, TFIIH level was decreased by treatment with CSS and restored in the presence of proteasome inhibitor, indicating that the degradation of NER proteins might be the cause of the inhibition of NER-protein recruitment. These results supported our hypothesis that aldehydes in CSS are the main contributor for the NER inhibition via protein degradation, and reconfirmed that exposure to CSS without filtration could be a severe threat to human health.