Evidence map›Paper›PMID 31562312›Full record

ArticleNature communications2019

Molecular basis of microhomology-mediated end-joining by purified full-length Polθ.

Samuel J Black, Ahmet Y Ozdemir, Ekaterina Kashkina, Tatiana Kent, Timur Rusanov, Dejan Ristic, Yeonoh Shin, Antonio Suma, Trung Hoang, Gurushankar Chandramouly and 9 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. 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 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

83 citing papers in PubMed, 111 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Impact of germlineMolecular therapy. Oncology · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Coordinated transfer of DNA between Pol θ and Pol δ resets microhomology choice during double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Defective Microhomology-Mediated End-joining in SMARCB1-Deficient Tumors.bioRxiv : the preprint server for biology · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 2 countries.

Samuel J BlackFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.ORCID http://orcid.org/0000-0001-5222-9024
Ahmet Y OzdemirFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Ekaterina KashkinaFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Tatiana KentFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Timur RusanovFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Dejan RisticDepartment of Molecular Genetics and Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands.
Yeonoh ShinDepartment of Biochemistry and Molecular Biology, The Center for RNA Molecular Biology, Pennsylvania State University, University Park, PA, 16802, USA.
Antonio SumaInstitute for Computational Molecular Science, Temple University, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5049-9255
Trung HoangFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Gurushankar ChandramoulyFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Labiba A SiddiqueFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Nikita BorisonnikFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Katherine Sullivan-ReedFels Institute for Cancer Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Joseph S MallonFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Tomasz SkorskiFels Institute for Cancer Research, Department of Microbiology and Immunology, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.ORCID http://orcid.org/0000-0002-3809-4538
Vincenzo CarnevaleInstitute for Computational Molecular Science, Temple University, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1918-8280
Katsuhiko S MurakamiDepartment of Biochemistry and Molecular Biology, The Center for RNA Molecular Biology, Pennsylvania State University, University Park, PA, 16802, USA.ORCID http://orcid.org/0000-0003-2244-0501
Claire WymanDepartment of Molecular Genetics and Department of Radiation Oncology, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands.
Richard T PomerantzFels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA. richard.pomerantz@temple.edu.
Temple University · USErasmus MC · NLPennsylvania State University · US

Funding

Targeting DNA repair to eradicate TKi-refractory/resistant CML and Ph+ALLR01CA186238 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI SKORSKI, TOMASZ · 2014 to 2024
$4.5M
X-Ray Crystallographic Studies of Multi-Subunit Nucleic Acid PolymerasesR01GM087350 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI MURAKAMI, KATSUHIKO · 2010 to 2018
$2.6M
Mechanisms of Mammalian Double-Strand Break RepairR01GM115472 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI POMERANTZ, RICHARD T · 2015 to 2019
$1.6M
Structure and Function of DNA Polymerase ThetaR01GM130889 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI POMERANTZ, RICHARD T · 2019 to 2022
$1.6M
NCI NIH HHS R01 CA186238NIGMS NIH HHS R01 GM087350NIGMS NIH HHS R01 GM115472NIGMS NIH HHS R01 GM130889
6 · The paper itself

Abstract

DNA polymerase θ (Polθ) is a unique polymerase-helicase fusion protein that promotes microhomology-mediated end-joining (MMEJ) of DNA double-strand breaks (DSBs). How full-length human Polθ performs MMEJ at the molecular level remains unknown. Using a biochemical approach, we find that the helicase is essential for Polθ MMEJ of long ssDNA overhangs which model resected DSBs. Remarkably, Polθ MMEJ of ssDNA overhangs requires polymerase-helicase attachment, but not the disordered central domain, and occurs independently of helicase ATPase activity. Using single-particle microscopy and biophysical methods, we find that polymerase-helicase attachment promotes multimeric gel-like Polθ complexes that facilitate DNA accumulation, DNA synapsis, and MMEJ. We further find that the central domain regulates Polθ multimerization and governs its DNA substrate requirements for MMEJ. These studies identify unexpected functions for the helicase and central domain and demonstrate the importance of polymerase-helicase tethering in MMEJ and the structural organization of Polθ.

Indexed as

DNA Breaks, Double-StrandedCatalytic DomainDNA-Binding ProteinsDNA BreaksDNA-Directed DNA PolymeraseDNA End-Joining RepairDNA HelicasesDNA Polymerase thetaDNA, Single-StrandedHumansModels, MolecularMutagenesis, Site-DirectedDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA HelicasesDNA Polymerase thetaDNA, Single-Stranded

Identifiers

PMID31562312
PMCPMC6764996
OpenAlexW2977140302

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.