Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine

Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine

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 dis...

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Main Authors: Joseph W. George, Mika Bessho, Tadayoshi Bessho
Format: Article
Language:English
Published: Hindawi Limited 2019-01-01
Series:Journal of Nucleic Acids
Online Access:http://dx.doi.org/10.1155/2019/6357609
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spelling doaj-1be73d07d6e4471180266752fa1a5e7f2020-11-25T02:36:52ZengHindawi LimitedJournal of Nucleic Acids2090-02012090-021X2019-01-01201910.1155/2019/63576096357609Inactivation of XPF Sensitizes Cancer Cells to GemcitabineJoseph W. George0Mika Bessho1Tadayoshi Bessho2The Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USAThe Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USAThe Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USAGemcitabine (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.http://dx.doi.org/10.1155/2019/6357609
collection DOAJ
language English
format Article
sources DOAJ
author Joseph W. George
Mika Bessho
Tadayoshi Bessho
spellingShingle Joseph W. George
Mika Bessho
Tadayoshi Bessho
Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine
Journal of Nucleic Acids
author_facet Joseph W. George
Mika Bessho
Tadayoshi Bessho
author_sort Joseph W. George
title Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine
title_short Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine
title_full Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine
title_fullStr Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine
title_full_unstemmed Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine
title_sort inactivation of xpf sensitizes cancer cells to gemcitabine
publisher Hindawi Limited
series Journal of Nucleic Acids
issn 2090-0201
2090-021X
publishDate 2019-01-01
description 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.
url http://dx.doi.org/10.1155/2019/6357609
work_keys_str_mv AT josephwgeorge inactivationofxpfsensitizescancercellstogemcitabine
AT mikabessho inactivationofxpfsensitizescancercellstogemcitabine
AT tadayoshibessho inactivationofxpfsensitizescancercellstogemcitabine
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