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

ChemBioChem - Tập 12 Số 7 - Trang 1115-1123 - 2011
Nora Kulak1, Wee Han Ang2, Guangyu Zhu2, MyatNoeZin Myint2, Stephen J. Lippard2
1Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
2Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA), Fax: (+1) 617‐258‐8150

Tóm tắt

AbstractResistance 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.

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