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oai:repisalud.isciii.es:20.500.12105/253582025-12-18T13:00:51Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991
Repisalud author Olivieri, Michele author Cho, Tiffany author Álvarez-Quilón, Alejandro author Li, Kejiao author Schellenberg, Matthew J author Zimmermann, Michal author Hustedt, Nicole author Rossi, Silvia Emma author Adam, Salomé author Melo, Henrique author Heijink, Anne Margriet author Sastre-Moreno, Guillermo author Moatti, Nathalie author Szilard, Rachel K author McEwan, Andrea author Ling, Alexanda K author Serrano-Benitez, Almudena author Ubhi, Tajinder author Feng, Sumin author Pawling, Judy author Delgado-Sainz, Irene author Ferguson, Michael W author Dennis, James W author Brown, Grant W author Cortes-Ledesma, Felipe author Williams, R Scott author Martin, Alberto author Xu, Dongyi author Durocher, Daniel author Olivieri, Michele author Cho, Tiffany author Álvarez-Quilón, Alejandro author Li, Kejiao author Schellenberg, Matthew J author Zimmermann, Michal author Hustedt, Nicole author Rossi, Silvia Emma author Adam, Salomé author Melo, Henrique author Heijink, Anne Margriet author Sastre-Moreno, Guillermo author Moatti, Nathalie author Szilard, Rachel K author McEwan, Andrea author Ling, Alexanda K author Serrano-Benitez, Almudena author Ubhi, Tajinder author Feng, Sumin author Pawling, Judy author Delgado-Sainz, Irene author Ferguson, Michael W author Dennis, James W author Brown, Grant W author Williams, R Scott author Martin, Alberto author Xu, Dongyi author Durocher, Daniel funder EMBO funder Unión Europea. Comisión Europea. European Research Council (ERC) funder Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) funder Canadian Institutes of Health Research (CIHR) funder Canadian Cancer Society (CCS) funder Krembil Foundation 2024-10-29T08:45:23Z 2024-10-29T08:45:23Z 2020-07-23 Cell . 2020 Jul 23;182(2):481-496.e21. https://hdl.handle.net/20.500.12105/25358 32649862 Cell https://pmc.ncbi.nlm.nih.gov/articles/PMC7384976/pdf/nihms-1598385.pdf The response to DNA damage is critical for cellular homeostasis, tumor suppression, immunity, and gametogenesis. In order to provide an unbiased and global view of the DNA damage response in human cells, we undertook 31 CRISPR-Cas9 screens against 27 genotoxic agents in the retinal pigment epithelium-1 (RPE1) cell line. These screens identified 890 genes whose loss causes either sensitivity or resistance to DNA-damaging agents. Mining this dataset, we discovered that ERCC6L2 (which is mutated in a bone-marrow failure syndrome) codes for a canonical non-homologous end-joining pathway factor, that the RNA polymerase II component ELOF1 modulates the response to transcription-blocking agents, and that the cytotoxicity of the G-quadruplex ligand pyridostatin involves trapping topoisomerase II on DNA. This map of the DNA damage response provides a rich resource to study this fundamental cellular system and has implications for the development and use of genotoxic agents in cancer therapy. eng CRISPR DNA damage DNA repair DNA-damaging agents cancer therapeutics functional genomics genome stability mechanism-of-action A Genetic Map of the Response to DNA Damage in Human Cells. research article 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 URL https://repisalud.isciii.es/bitstreams/ead4befe-2b22-4ad6-a647-ea9557292005/download File MD5 ab1011e13c0d14aaab4fd79096d03afe 154037 application/vnd.openxmlformats-officedocument.wordprocessingml.document Nature-BTCA cnio.docx URL https://repisalud.isciii.es/bitstreams/162f34db-3bb3-4669-99f3-39ef0922b128/download File MD5 f1e14bf167db8ba0026351b8ad3fdf44 5619 text/plain Nature-BTCA cnio.docx.txt