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A Genetic Map of the Response to DNA Damage in Human Cells.
Olivieri, Michele; Cho, Tiffany; Álvarez-Quilón, Alejandro; Li, Kejiao; Schellenberg, Matthew J; Zimmermann, Michal; Hustedt, Nicole; Rossi, Silvia Emma; Adam, Salomé; Melo, Henrique; Heijink, Anne Margriet; Sastre-Moreno, Guillermo; Moatti, Nathalie; Szilard, Rachel K; McEwan, Andrea; Ling, Alexanda K; Serrano-Benitez, Almudena; Ubhi, Tajinder; Feng, Sumin; Pawling, Judy; Delgado-Sainz, Irene; Ferguson, Michael W; Dennis, James W; Brown, Grant W; Cortés-Ledesma, Felipe; Williams, R Scott; Martin, Alberto; Xu, Dongyi; Durocher, Daniel.
Afiliação
  • Olivieri M; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
  • Cho T; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
  • Álvarez-Quilón A; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Li K; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871 Beijing, China.
  • Schellenberg MJ; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, USA.
  • Zimmermann M; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Hustedt N; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Rossi SE; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Adam S; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Melo H; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Heijink AM; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Sastre-Moreno G; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Moatti N; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Szilard RK; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • McEwan A; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Ling AK; Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, ON, M5S 1A8, Canada.
  • Serrano-Benitez A; Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), CSIC-Universidad de Sevilla Universidad Pablo de Olavide, 41092 Sevilla, Spain.
  • Ubhi T; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
  • Feng S; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Pawling J; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Delgado-Sainz I; Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), CSIC-Universidad de Sevilla Universidad Pablo de Olavide, 41092 Sevilla, Spain.
  • Ferguson MW; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
  • Dennis JW; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
  • Brown GW; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
  • Cortés-Ledesma F; Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), CSIC-Universidad de Sevilla Universidad Pablo de Olavide, 41092 Sevilla, Spain.
  • Williams RS; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC 27709, USA.
  • Martin A; Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, ON, M5S 1A8, Canada.
  • Xu D; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871 Beijing, China.
  • Durocher D; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: durocher@lunenfeld.ca.
Cell ; 182(2): 481-496.e21, 2020 07 23.
Article em En | MEDLINE | ID: mdl-32649862
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Redes Reguladoras de Genes Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Redes Reguladoras de Genes Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Canadá