Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine

Joseph W. George, Mika Bessho, Tadayoshi Bessho

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number6357609
JournalJournal of Nucleic Acids
Volume2019
DOIs
StatePublished - Jan 1 2019

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gemcitabine
Cells
Repair
Neoplasms
DNA
DNA Repair
DNA Damage
DNA-(Apurinic or Apyrimidinic Site) Lyase
Deoxycytidine
Endonucleases
Cytotoxicity
DNA Replication
Pancreatic Neoplasms
Nucleotides

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine. / George, Joseph W.; Bessho, Mika; Bessho, Tadayoshi.

In: Journal of Nucleic Acids, Vol. 2019, 6357609, 01.01.2019.

Research output: Contribution to journalArticle

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