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Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine.

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.

SUBMITTER: George JW

PROVIDER: S-EPMC6421022 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine.

George Joseph W JW Bessho Mika M Bessho Tadayoshi T

Journal of nucleic acids 20190303

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 identif ...[more]

PMID: 30941207

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Correction: Intracellular STING inactivation sensitizes breast cancer cells to genotoxic agents.

Project description:[This corrects the article DOI: 10.18632/oncotarget.12858.].

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