2013-07-01
Caffeine suppresses homologous recombination through interference with RAD51-mediated joint molecule formation
Publication
Publication
Nucleic Acids Research , Volume 41 - Issue 13 p. 6475- 6489
Caffeine is a widely used inhibitor of the protein kinases that play a central role in the DNA damage response. We used chemical inhibitors and genetically deficient mouse embryonic stem cell lines to study the role of DNA damage response in stable integration of the transfected DNA and found that caffeine rapidly, efficiently and reversibly inhibited homologous integration of the transfected DNA as measured by several homologous recombination-mediated gene-targeting assays. Biochemical and structural biology experiments revealed that caffeine interfered with a pivotal step in homologous recombination, homologous joint molecule formation, through increasing interactions of the RAD51 nucleoprotein filament with non-homologous DNA. Our results suggest that recombination pathways dependent on extensive homology search are caffeine-sensitive and stress the importance of considering direct checkpoint-independent mechanisms in the interpretation of the effects of caffeine on DNA repair.
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| doi.org/10.1093/nar/gkt375, hdl.handle.net/1765/54325 | |
| Nucleic Acids Research | |
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| Organisation | Department of Radiation Oncology |
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Zelensky, A., Sanchez, H., Ristic, D., Vidic, I., van Rossum-Fikkert, S., Essers, J., … Kanaar, R. (2013). Caffeine suppresses homologous recombination through interference with RAD51-mediated joint molecule formation. Nucleic Acids Research, 41(13), 6475–6489. doi:10.1093/nar/gkt375 |
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