This is due to spironolactone reversibly inducing the degradation of XPB in a ubiquitin-activating enzyme- and proteasome-dependent manner, impairing both basal and activated mRNA transcription of the transcription/repair factor TFIIH.374,375 In agreement with this, a recent study also demonstrated that spironolactone could inhibit SIRT2-mediated transcription-coupled nucleotide excision repair, disturbing cisplatin-induced DNA crosslinks in lung cancer.376 In addition, the function of spironolactone on reducing homology directed repair frequencies was confirmed. This evidence concerns the gene ERCC3 and lung cancer.