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Updated: Sep 20, 2026

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
Selective targeting of homologous DNA recombination repair by gemcitabine
Floris M Wachters1, John W G van Putten, Jan G Maring
1Department of Pulmonary Diseases, University Hospital Groningen, Groningen, The Netherlands. f.m.wachters@int.azg.nl
Purpose:
Gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) is a potent radiosensitizer. The mechanism of dFdC-mediated radiosensitization is yet poorly understood. We recently excluded inhibition of DNA double-strand break (DSB) repair by nonhomologous end-joining (NHEJ) as a means of radiosensitization. In the current study, we addressed the possibility that dFdC might affect homologous recombination (HR)-mediated DSB repair or base excision repair (BER).
Methods And Materials:
DFdC-mediated radiosensitization in cell lines deficient in BER and in HR was compared with that in their BER-proficient and HR-proficient parental counterparts. Sensitization to mitomycin C (MMC) was also investigated in cell lines deficient and proficient in HR. Additionally, the effect of dFdC on Rad51 foci formation after irradiation was studied.
Results:
DFdC did induce radiosensitization in BER-deficient cells; however, the respective mutant cells deficient in HR did not show dFdC-mediated radiosensitization. In HR-proficient, but not in HR-deficient, cells dFdC also induced substantial enhancement of the cytotoxic effect of MMC. Finally, we found that dFdC interferes with Rad51 foci formation after irradiation.
Conclusion:
DFdC causes radiosensitization by specific interference with HR.
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