Role of Endonucleases XPF and XPG in Nucleotide Excision Repair of Platinated DNA and Cisplatin/Oxaliplatin Cytotoxicity

Resistance of tumor cells to platinum anticancer agents poses a major problem in cancer chemotherapy. One of the mechanisms associated with platinum-based drug resistance is the enhanced capacity of the cell to carry out nucleotide excision repair (NER) on platinum-damaged DNA. Endonucleases XPF and XPG are critical components of NER, responsible for excising the damaged DNA strand to remove the DNA lesion. Here, we investigated possible consequences of down-regulation of XPF and XPG gene expression in osteosarcoma cancer cells (U2OS) and the impact on cellular transcription and DNA repair. We further evaluated the sensitivity of such cells toward the platinum anticancer drugs cisplatin and oxaliplatin. Knockdown of endonucleases: One of the mechanisms associated with platinum-based drug resistance is the enhanced excision repair activity on platinum-damaged DNA. Inhibiting endonuclease activity by the repair complex by using RNAi knockdown (see figure) impacted transcription efficiency through platinum-DNA lesions and cellular sensitivity to platinum anticancer agents. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.