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Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine.

Joseph W GeorgeMika BesshoTadayoshi Bessho
Published in: Journal of nucleic acids (2019)
Gemcitabine (2', 2'-difluorodeoxycytidine; dFdC) is a deoxycytidine analog and is used primarily against pancreatic cancer. The cytotoxicity of gemcitabine is due to the inhibition of DNA replication. However, a mechanism of removal of the incorporated dFdC is largely unknown. In this report, we discovered that nucleotide excision repair protein XPF-ERCC1 participates in the repair of gemcitabine-induced DNA damage and inactivation of XPF sensitizes cells to gemcitabine. Further analysis identified that XPF-ERCC1 functions together with apurinic/apyrimidinic endonuclease (APE) in the repair of gemcitabine-induced DNA damage. Our results demonstrate the importance of the evaluation of DNA repair activities in gemcitabine treatment.
Keyphrases
  • dna repair
  • dna damage
  • locally advanced
  • induced apoptosis
  • oxidative stress
  • squamous cell carcinoma
  • diabetic rats
  • radiation therapy
  • rectal cancer
  • small molecule
  • cell death
  • protein protein
  • amino acid