Evidence map›Paper›PMID 33606978›Full record

ArticleCell2021

Functional interrogation of DNA damage response variants with base editing screens.

Raquel Cuella-Martin, Samuel B Hayward, Xiao Fan, Xiao Chen, Jen-Wei Huang, Angelo Taglialatela, Giuseppe Leuzzi, Junfei Zhao, Raul Rabadan, Chao Lu and 2 more

Open access · greenAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed
16.0field-weighted citation impact, top 1% of its field
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

175 citing papers in PubMed, 249 citations in OpenAlex.

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  18. Scaling perturbations: beyond genome-scale CRISPR screens.bioRxiv : the preprint server for biology · 2026
    Article
  19. Article
  20. Genes & diseases · 2026
    Review

115 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Raquel Cuella-MartinDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Samuel B HaywardDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Xiao FanDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Xiao ChenDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jen-Wei HuangDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Angelo TaglialatelaDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Giuseppe LeuzziDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Junfei ZhaoDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY 10032, USA; Program for Mathematical Genomics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Raul RabadanDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY 10032, USA; Program for Mathematical Genomics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Chao LuDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Yufeng ShenDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Alberto CicciaDepartment of Genetics and Development, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: ac3685@cumc.columbia.edu.
Columbia University Irving Medical Center · US

Funding

The Role of CTIP in Lymphocyte Development and LymphomagenesisP01CA174653 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI RABADAN, RAUL · 2014 to 2024
$17.6M
Replication fork remodeling and genomic stabilityR01CA197774 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Alberto Ciccia · 2016 to 2026
$4.2M
Restoring genome stability and tumor suppression in BRCA1 deficient cellsR01CA227450 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BAER, RICHARD J, CICCIA, ALBERTO · 2019 to 2022
$2.1M
NCI NIH HHS P01 CA174653NCI NIH HHS R01 CA197774NCI NIH HHS R01 CA227450
6 · The paper itself

Abstract

Mutations in DNA damage response (DDR) genes endanger genome integrity and predispose to cancer and genetic disorders. Here, using CRISPR-dependent cytosine base editing screens, we identify > 2,000 sgRNAs that generate nucleotide variants in 86 DDR genes, resulting in altered cellular fitness upon DNA damage. Among those variants, we discover loss- and gain-of-function mutants in the Tudor domain of the DDR regulator 53BP1 that define a non-canonical surface required for binding the deubiquitinase USP28. Moreover, we characterize variants of the TRAIP ubiquitin ligase that define a domain, whose loss renders cells resistant to topoisomerase I inhibition. Finally, we identify mutations in the ATM kinase with opposing genome stability phenotypes and loss-of-function mutations in the CHK2 kinase previously categorized as variants of uncertain significance for breast cancer. We anticipate that this resource will enable the discovery of additional DDR gene functions and expedite studies of DDR variants in human disease.

Indexed as

DNA DamageGene EditingGenetic TestingAmino Acid SequenceAtaxia Telangiectasia Mutated ProteinsBase SequenceCamptothecinCell LineCRISPR-Cas SystemsDNA RepairFemaleHumansMutationPhenotypeProtein BindingProtein DomainsAtaxia Telangiectasia Mutated ProteinsCamptothecinRNA, Guide, CRISPR-Cas SystemsTopoisomerase InhibitorsTP53BP1 protein, humanTRAIP protein, humanTumor Suppressor p53-Binding Protein 1Ubiquitin-Protein LigasesUbiquitin ThiolesteraseUSP28 protein, human53BP1ATMBE3 base editorCHK2clinically relevant variantsCRISPR-dependent base editingDNA damage responseTRAIPvariants of uncertain significance

Identifiers

PMID33606978
PMCPMC8018281
OpenAlexW3131839988

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.