RT Journal Article
T1 A Genetic Map of the Response to DNA Damage in Human Cells.
A1 Olivieri, Michele
A1 Cho, Tiffany
A1 Álvarez-Quilón, Alejandro
A1 Li, Kejiao
A1 Schellenberg, Matthew J
A1 Zimmermann, Michal
A1 Hustedt, Nicole
A1 Rossi, Silvia Emma
A1 Adam, Salomé
A1 Melo, Henrique
A1 Heijink, Anne Margriet
A1 Sastre-Moreno, Guillermo
A1 Moatti, Nathalie
A1 Szilard, Rachel K
A1 McEwan, Andrea
A1 Ling, Alexanda K
A1 Serrano-Benitez, Almudena
A1 Ubhi, Tajinder
A1 Feng, Sumin
A1 Pawling, Judy
A1 Delgado-Sainz, Irene
A1 Ferguson, Michael W
A1 Dennis, James W
A1 Brown, Grant W
A1 Cortés-Ledesma, Felipe
A1 Williams, R Scott
A1 Martin, Alberto
A1 Xu, Dongyi
A1 Durocher, Daniel
K1 CRISPR
K1 DNA damage
K1 DNA repair
K1 DNA-damaging agents
K1 cancer therapeutics
K1 functional genomics
K1 genome stability
K1 mechanism-of-action
AB 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.
YR 2020
FD 2020-07-09
LK http://hdl.handle.net/10668/15917
UL http://hdl.handle.net/10668/15917
LA en
DS RISalud
RD Apr 11, 2025