Evidence map›Paper›PMID 37541219›Full record

ArticleMolecular cell2023

FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.

Min Huang, Fuwen Yao, Litong Nie, Chao Wang, Dan Su, Huimin Zhang, Siting Li, Mengfan Tang, Xu Feng, Bin Yu and 6 more

Abstract read
In one paragraph

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed.

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  19. Review
  20. Genome Instability Induced by Topoisomerase Misfunction.International journal of molecular sciences · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Min HuangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Fuwen YaoDepartment of Hepatopancreatobiliary Surgery, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Litong NieDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Chao WangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Dan SuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Huimin ZhangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Siting LiDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mengfan TangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xu FengDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Bin YuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zhen ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Shimin WangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ling YinDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lisha MouDepartment of Hepatopancreatobiliary Surgery, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Traver HartDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Junjie ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jchen8@mdanderson.org.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Project 4: Coordinating Nucleolytic Pathways During Crosslink RepairP01CA193124 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WOOD, RICHARD D · 2017 to 2022
$9.6M
Exploring DNA damage response pathways as targets for cancer therapyR35CA274234 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Junjie Chen · 2022 to 2026
$4.4M
High-content microscopy platform for multiplex perturbation/multiplex readout studiesR35GM130119 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Traver Hart · 2018 to 2026
$3.9M
Deciphering pathways involved in topoisomerase II turnoverR01CA275712 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Junjie Chen · 2023 to 2026
$2.0M
Elucidating mechanisms underlying replication checkpoint controlR01CA278758 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Junjie Chen · 2023 to 2026
$2.0M
Novel regulations of DNA damage repairR01CA216911 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, JUNJIE · 2017 to 2021
$1.8M
53BP1-dependent pathway in DNA repairR01CA216437 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, JUNJIE · 2017 to 2022
$1.8M
Define redundant functions of H2AX and NBS1 in DNA repairR01CA210929 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, JUNJIE · 2017 to 2022
$1.8M
NCI NIH HHS P01 CA193124NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA210929NCI NIH HHS R01 CA216437NCI NIH HHS R01 CA216911NCI NIH HHS R01 CA275712NCI NIH HHS R01 CA278758NCI NIH HHS R35 CA274234NIGMS NIH HHS R35 GM130119
6 · The paper itself

Abstract

DNA damage-activated signaling pathways are critical for coordinating multiple cellular processes, which must be tightly regulated to maintain genome stability. To provide a comprehensive and unbiased perspective of DNA damage response (DDR) signaling pathways, we performed 30 fluorescence-activated cell sorting (FACS)-based genome-wide CRISPR screens in human cell lines with antibodies recognizing distinct endogenous DNA damage signaling proteins to identify critical regulators involved in DDR. We discovered that proteasome-mediated processing is an early and prerequisite event for cells to trigger camptothecin- and etoposide-induced DDR signaling. Furthermore, we identified PRMT1 and PRMT5 as modulators that regulate ATM protein level. Moreover, we discovered that GNB1L is a key regulator of DDR signaling via its role as a co-chaperone specifically regulating PIKK proteins. Collectively, these screens offer a rich resource for further investigation of DDR, which may provide insight into strategies of targeting these DDR pathways to improve therapeutic outcomes.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsDNA DamageAtaxia Telangiectasia Mutated ProteinsFlow CytometryGenomeHumansProtein-Arginine N-MethyltransferasesRepressor ProteinsSignal TransductionAtaxia Telangiectasia Mutated ProteinsPRMT1 protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesRepressor ProteinsantibodyDDR signalingFACS-based CRISPR screenGNB1LPRMT5proteasome

Identifiers

PMID37541219
PMCPMC10421629

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.