The requirement of yeast Ssl2 (Rad25) for the repair of cisplatin-damaged DNA.
Cisplatin is one of the most widely used anticancer agents. Cisplatin-induced cytotoxicity results from its ability to form cisplatin-DNA adducts within the cellular genome which can inhibit the transcription of genes and the replication of DNA. Cisplatin-adducts are primarily removed by the nucleotide excision repair (NER) pathway. The SSL2 (RAD25) gene of Saccharomyces cerevisiae, a homolog of the XPB (ERCC3) gene in humans, is involved in the nucleotide excision repair of UV-damaged DNA and is also required for cell viability. However, the role of Ssl2 (Rad25) in cisplatin sensitivity has not been examined. In this study, we have demonstrated that a yeast strain carrying the mutant allele SSL2-XP, a truncated form of SSL2 (RAD25) at the carboxyl terminus to mimic the human XPB (ERCC3) mutation, has increased cellular sensitivity to cisplatin in comparison to wild type cells. Analysis by host cell reactivation (HCR) assay further shows that Ssl2 (Rad25) is required for the repair of cisplatin-damaged DNA.
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, 08901, USA.
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D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D018736:DNA Adducts / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004271:DNA, Fungal / Q000187:drug effects / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D006801:Humans; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D051758:Transcription Factor TFIIH
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004271:DNA, Fungal; D005656:Fungal Proteins; C489575:SSL2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D051758:Transcription Factor TFIIH; D004265:DNA Helicases; D002945:Cisplatin