Get access

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

Authors

  • Dr. Nora Graf,

    1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA), Fax: (+1) 617-258-8150
    Search for more papers by this author
  • Dr. Wee Han Ang,

    1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA), Fax: (+1) 617-258-8150
    Search for more papers by this author
  • Dr. Guangyu Zhu,

    1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA), Fax: (+1) 617-258-8150
    Search for more papers by this author
  • MyatNoeZin Myint,

    1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA), Fax: (+1) 617-258-8150
    Search for more papers by this author
  • Prof. Stephen J. Lippard

    Corresponding author
    1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA), Fax: (+1) 617-258-8150
    • Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA), Fax: (+1) 617-258-8150
    Search for more papers by this author

Abstract

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.

Get access to the full text of this article

Ancillary