Evidence map›Paper›PMID 38640894›Full record

ArticleMolecular cell2024

Sequential requirements for distinct Polθ domains during theta-mediated end joining.

Carel Fijen, Lea Drogalis Beckham, Dante Terino, Yuzhen Li, Dale A Ramsden, Richard D Wood, Sylvie Doublié, Eli Rothenberg

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. DNA Repair Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  7. Article
  8. Review
  9. 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
  10. Article
  11. Making 3' ends meet.Nature structural & molecular biology · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Carel FijenDepartment of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address: carolus.fijen@nyulangone.org.
Lea Drogalis BeckhamDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Dante TerinoDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Yuzhen LiDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
Dale A RamsdenDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Richard D WoodDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
Sylvie DoubliéDepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Eli RothenbergDepartment of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address: eli.rothenberg@nyulangone.org.

Funding

Structural determinants of Pol theta functionP01CA247773 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DALE A RAMSDEN · 2020 to 2026
$15.2M
Mechanisms of Human DNA Double-Strand Break Repair via Quantitative Single-Molecule Imaging - Equipment SupplementR35GM134947 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Eli Rothenberg · 2020 to 2026
$3.4M
Mechanism and Fidelity of RAG mediated DNA recombinationR01AI153040 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ROTHENBERG, ELI · 2020 to 2024
$2.7M
NCI NIH HHS P01 CA247773NIAID NIH HHS R01 AI153040NIGMS NIH HHS R35 GM134947
6 · The paper itself

Abstract

DNA polymerase θ (Polθ) plays a central role in a DNA double-strand break repair pathway termed theta-mediated end joining (TMEJ). TMEJ functions by pairing short-sequence "microhomologies" (MHs) in single-stranded DNA at each end of a break and subsequently initiating DNA synthesis. It is not known how the Polθ helicase domain (HD) and polymerase domain (PD) operate to bring together MHs and facilitate repair. To resolve these transient processes in real time, we utilized in vitro single-molecule FRET approaches and biochemical analyses. We find that the Polθ-HD mediates the initial capture of two ssDNA strands, bringing them in close proximity. The Polθ-PD binds and stabilizes pre-annealed MHs to form a synaptic complex (SC) and initiate repair synthesis. Individual synthesis reactions show that Polθ is inherently non-processive, accounting for complex mutational patterns during TMEJ. Binding of Polθ-PD to stem-loop-forming sequences can substantially limit synapsis, depending on the available dNTPs and sequence context.

Indexed as

DNA Breaks, Double-StrandedDNA-Directed DNA PolymeraseDNA End-Joining RepairDNA HelicasesDNA ReplicationDNA, Single-StrandedDNA-Directed DNA PolymeraseDNA HelicasesDNA, Single-StrandedDNA polymerase thetaDNA repairdouble-strand breakshelicasemicrohomologyPolθsingle-molecule FRETstem-loopsTMEJ

Identifiers

PMID38640894
PMCPMC11031631

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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.