A Genetic Map of the Response to DNA Damage in Human Cells
Copyright © 2020 Elsevier Inc. All rights reserved..
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.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:182 |
|---|---|
| Enthalten in: |
Cell - 182(2020), 2 vom: 23. Juli, Seite 481-496.e21 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Olivieri, Michele [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.04.2021 Date Revised 04.01.2024 published: Print-Electronic CommentIn: Fac Rev. 2022 Nov 21;11:35. - PMID 36532708 Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.cell.2020.05.040 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM312266146 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM312266146 | ||
| 003 | DE-627 | ||
| 005 | 20240108141518.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.cell.2020.05.040 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1248.xml |
| 035 | |a (DE-627)NLM312266146 | ||
| 035 | |a (NLM)32649862 | ||
| 035 | |a (PII)S0092-8674(20)30673-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Olivieri, Michele |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Genetic Map of the Response to DNA Damage in Human Cells |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.04.2021 | ||
| 500 | |a Date Revised 04.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Fac Rev. 2022 Nov 21;11:35. - PMID 36532708 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CRISPR | |
| 650 | 4 | |a DNA damage | |
| 650 | 4 | |a DNA repair | |
| 650 | 4 | |a DNA-damaging agents | |
| 650 | 4 | |a cancer therapeutics | |
| 650 | 4 | |a functional genomics | |
| 650 | 4 | |a genome stability | |
| 650 | 4 | |a mechanism-of-action | |
| 650 | 7 | |a Aminoquinolines |2 NLM | |
| 650 | 7 | |a Picolinic Acids |2 NLM | |
| 650 | 7 | |a RNA, Guide, CRISPR-Cas Systems |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 650 | 7 | |a pyridostatin |2 NLM | |
| 650 | 7 | |a Cytochrome-B(5) Reductase |2 NLM | |
| 650 | 7 | |a EC 1.6.2.2 |2 NLM | |
| 650 | 7 | |a DNA Helicases |2 NLM | |
| 650 | 7 | |a EC 3.6.4.- |2 NLM | |
| 650 | 7 | |a ERCC6L2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.6.4.12 |2 NLM | |
| 650 | 7 | |a DNA Topoisomerases, Type II |2 NLM | |
| 650 | 7 | |a EC 5.99.1.3 |2 NLM | |
| 700 | 1 | |a Cho, Tiffany |e verfasserin |4 aut | |
| 700 | 1 | |a Álvarez-Quilón, Alejandro |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Kejiao |e verfasserin |4 aut | |
| 700 | 1 | |a Schellenberg, Matthew J |e verfasserin |4 aut | |
| 700 | 1 | |a Zimmermann, Michal |e verfasserin |4 aut | |
| 700 | 1 | |a Hustedt, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Rossi, Silvia Emma |e verfasserin |4 aut | |
| 700 | 1 | |a Adam, Salomé |e verfasserin |4 aut | |
| 700 | 1 | |a Melo, Henrique |e verfasserin |4 aut | |
| 700 | 1 | |a Heijink, Anne Margriet |e verfasserin |4 aut | |
| 700 | 1 | |a Sastre-Moreno, Guillermo |e verfasserin |4 aut | |
| 700 | 1 | |a Moatti, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Szilard, Rachel K |e verfasserin |4 aut | |
| 700 | 1 | |a McEwan, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Alexanda K |e verfasserin |4 aut | |
| 700 | 1 | |a Serrano-Benitez, Almudena |e verfasserin |4 aut | |
| 700 | 1 | |a Ubhi, Tajinder |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Sumin |e verfasserin |4 aut | |
| 700 | 1 | |a Pawling, Judy |e verfasserin |4 aut | |
| 700 | 1 | |a Delgado-Sainz, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Ferguson, Michael W |e verfasserin |4 aut | |
| 700 | 1 | |a Dennis, James W |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Grant W |e verfasserin |4 aut | |
| 700 | 1 | |a Cortés-Ledesma, Felipe |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, R Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Alberto |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Dongyi |e verfasserin |4 aut | |
| 700 | 1 | |a Durocher, Daniel |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell |d 1974 |g 182(2020), 2 vom: 23. Juli, Seite 481-496.e21 |w (DE-627)NLM000088935 |x 1097-4172 |7 nnns |
| 773 | 1 | 8 | |g volume:182 |g year:2020 |g number:2 |g day:23 |g month:07 |g pages:481-496.e21 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.cell.2020.05.040 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 182 |j 2020 |e 2 |b 23 |c 07 |h 481-496.e21 | ||