Evidence map›Paper›PMID 34197737›Full record

ArticleMolecular cell2021

EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart.

Shashank Hambarde, Chi-Lin Tsai, Raj K Pandita, Albino Bacolla, Anirban Maitra, Vijay Charaka, Clayton R Hunt, Rakesh Kumar, Oliver Limbo, Remy Le Meur and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  14. Structure, function and evolution of the bacterial DinG-like proteins.Computational and structural biotechnology journal · 2025
    Review
  15. Article
  16. Article
  17. Targeting ATR in patients with cancer.Nature reviews. Clinical oncology · 2024
    Review
  18. Article
  19. Article
  20. DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.Advances in experimental medicine and biology · 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 at 7 institutions in 2 countries.

Shashank HambardeDepartment of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Neurosurgery, The Houston Methodist Research Institute, Houston, TX 77030, USA.
Chi-Lin TsaiDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Raj K PanditaDepartment of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Albino BacollaDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anirban MaitraSheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Vijay CharakaDepartment of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX 77030, USA.
Clayton R HuntDepartment of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX 77030, USA.
Rakesh KumarSchool of Biotechnology, Shri Mata Vashino Devi University, Katra, Jammu and Kashmir, 182320, India.
Oliver LimboDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Remy Le MeurDepartments of Biochemistry and Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37240, USA.
Walter J ChazinDepartments of Biochemistry and Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37240, USA.
Susan E TsutakawaMolecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Paul RussellDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Katharina SchlacherDepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Tej K PanditaDepartment of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Neurosurgery, The Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: tej.pandita@bcm.edu.
John A TainerDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jtainer@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USHouston Methodist · USScripps Research Institute · USVanderbilt University · USBaylor College of Medicine · USLawrence Berkeley National Laboratory · USShri Mata Vaishno Devi University · IN

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WALTER J. CHAZIN · 2001 to 2026
$89.6M
User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI PAUL David ADAMS, Gregory L Hura · 2017 to 2026
$28.6M
Mesoscale and Nanoscale Technologies Integrated by Structures for DNA Repair Complexes (MANTIS-DRC)R35CA220430 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI John A. Tainer · 2018 to 2026
$7.6M
Structural Biology of Multi-Domain Proteins and Multi-Protein Machinery in DNA Replication and RepairR35GM118089 · NIGMS · VANDERBILT UNIVERSITY · PI WALTER J. CHAZIN · 2016 to 2026
$4.9M
The XPA scaffold protein in Nucleotide Excision RepairR01CA218315 · NCI · VANDERBILT UNIVERSITY · PI WALTER J. CHAZIN · 2018 to 2026
$3.4M
CHROMATIN MODIFYING FACTORS CONTROL RADIATION RESPONSE AND GENOMIC STABILITYR01CA129537 · NCI · WASHINGTON UNIVERSITY · PI PANDITA, TEJ K · 2008 to 2018
$3.3M
Eliminating Critical Systematic Errors In Structural Biology With Next-Generation SimulationR01GM124149 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HOLTON, JAMES M · 2017 to 2024
$2.5M
Mechanism of RAD51C fork protection and environmental carcinogenesisR01ES029680 · NIEHS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SCHLACHER, KATHARINA · 2018 to 2022
$1.8M
Functional Characterization of the Mammalian MOF Gene ProductR01CA123232 · NCI · WASHINGTON UNIVERSITY · PI PANDITA, TEJ K · 2007 to 2011
$1.5M
Role of Heterochromatin protein 1 Beta in Genome Maintenance and OncogenesisR01GM109768 · NIGMS · METHODIST HOSPITAL RESEARCH INSTITUTE · PI PANDITA, TEJ K · 2014 to 2017
$1.2M
NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA123232NCI NIH HHS R01 CA129537NCI NIH HHS R01 CA218315NCI NIH HHS R35 CA220430NIEHS NIH HHS R01 ES029680NIGMS NIH HHS P30 GM124169NIGMS NIH HHS R01 GM109768NIGMS NIH HHS R01 GM124149NIGMS NIH HHS R35 GM118089
6 · The paper itself

Abstract

Stalled DNA replication fork restart after stress as orchestrated by ATR kinase, BLM helicase, and structure-specific nucleases enables replication, cell survival, and genome stability. Here we unveil human exonuclease V (EXO5) as an ATR-regulated DNA structure-specific nuclease and BLM partner for replication fork restart. We find that elevated EXO5 in tumors correlates with increased mutation loads and poor patient survival, suggesting that EXO5 upregulation has oncogenic potential. Structural, mechanistic, and mutational analyses of EXO5 and EXO5-DNA complexes reveal a single-stranded DNA binding channel with an adjacent ATR phosphorylation motif (T88Q89) that regulates EXO5 nuclease activity and BLM binding identified by mass spectrometric analysis. EXO5 phospho-mimetic mutant rescues the restart defect from EXO5 depletion that decreases fork progression, DNA damage repair, and cell survival. EXO5 depletion furthermore rescues survival of FANCA-deficient cells and indicates EXO5 functions epistatically with SMARCAL1 and BLM. Thus, an EXO5 axis connects ATR and BLM in directing replication fork restart.

Indexed as

Ataxia Telangiectasia Mutated ProteinsCell LineCell Line, TumorDNADNA-Binding ProteinsDNA DamageDNA HelicasesDNA Mutational AnalysisDNA RepairDNA ReplicationExonucleasesGenomic InstabilityHEK293 CellsHeLa CellsHumansMutationAtaxia Telangiectasia Mutated ProteinsATR protein, humanBloom syndrome proteinDNADNA-Binding ProteinsDNA HelicasesEXO5 protein, humanExonucleasesRecQ HelicasesATR phosphorylationBloomexonucleaseFanconi anemiafork restartgenetic instabilityinterstrand crosslink repairreplication stressSCEsister chromatid exchangetumor proliferation

Identifiers

PMID34197737
PMCPMC8720176
OpenAlexW3176969249

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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.