Evidence map›Paper›PMID 40548939›Full record

ArticleNucleic acids research2025

USP37 counteracts HLTF to protect damaged replication forks and promote survival of BRCA1-deficient cells and PARP inhibitor resistance.

Mengfan Tang, Siting Li, Ziqiang Zhu, Chao Wang, Shuai Ding, Huimin Zhang, Min Huang, Sarah Keast, Zhen Chen, Ling Yin and 4 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Mengfan TangDepartment of Immunology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Siting LiDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Ziqiang ZhuDepartment of Immunology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Chao WangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Shuai DingDepartment of Immunology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Huimin ZhangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.ORCID 0000-0001-8987-6014
Min HuangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Sarah KeastDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Zhen ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Ling YinDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Litong NieDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Dan SuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Xu FengDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
Junjie ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.ORCID 0000-0002-1493-2189

Funding

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
Deciphering pathways involved in topoisomerase II turnoverR01CA275712 · 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
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
53BP1-dependent pathway in DNA repairR01CA216437 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, JUNJIE · 2017 to 2022
$1.8M
CPRIT RP160667CPRIT RP180813Jiangsu Specially Appointed Professorship FoundationNational Natural Science Foundation of China 82403439National Natural Science Foundation of China 82404048Natural Science Foundation of Jiangsu Province of China BK20240730Natural Science Foundation of Jiangsu Province of China BK20241138NCI NIH HHS P01 CA193124NCI NIH HHS R01 CA210929NCI NIH HHS R01 CA216437NCI NIH HHS R01 CA216911NCI NIH HHS R01 CA275712NCI NIH HHS R35 CA274234NIH HHS CA193124NIH HHS CA210929NIH HHS CA216437NIH HHS CA216911NIH HHS CA274234NIH HHS CA275712Pamela and Wayne Garrison Distinguished Chair in Cancer Research
6 · The paper itself

Abstract

Poly(ADP-ribose) polymerase inhibitors (PARPi) have greatly improved survival of cancer patients harboring BRCA1 mutations. However, therapy resistance develops via either restoration of homologous recombination or replication fork stabilization. Therapeutic targets to overcome PARPi resistance are critically needed. We identified the deubiquitinase USP37 as a key determinant of PARPi toxicity in BRCA1-deficient cells via whole-genome CRISPR screens. USP37 ablation enhanced PARPi sensitivity in BRCA1-deficient cells and also overcame PARPi resistance due to 53BP1 loss. USP37 interacts with and deubiquitinates replication protein A (RPA) at stalled replication forks to limit excessive RPA accumulation, progressive RPA exhaustion, and the conversion of RPA-coated single-stranded DNAs to DNA double-strand breaks. Moreover, USP37 limits helicase-like transcription factor (HLTF) accumulation at replication forks and thus prevents MRE11-dependent fork degradation upon replication stress. Depletion of HLTF reversed the replication-associated damage observed in USP37 knockout cells. Our data suggest that USP37 protects replication fork stability by counteracting HLTF function and promotes survival of BRCA1-deficient cells, making it a promising drug target to overcome PARPi resistance in BRCA1-deficient tumors.

Indexed as

BRCA1 ProteinDNA-Binding ProteinsDNA ReplicationDrug Resistance, NeoplasmPoly(ADP-ribose) Polymerase InhibitorsCell Line, TumorCell SurvivalDNA Breaks, Double-StrandedHumansMRE11 Homologue ProteinReplication Protein ATranscription FactorsTumor Suppressor p53-Binding Protein 1BRCA1 ProteinBRCA1 protein, humanDNA-Binding ProteinsHLTF protein, humanMRE11 Homologue ProteinPoly(ADP-ribose) Polymerase InhibitorsReplication Protein ATranscription FactorsTumor Suppressor p53-Binding Protein 1

Identifiers

PMID40548939
PMCPMC12205991

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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.