Evidence map›Paper›PMID 34522048›Full record

ReviewNature reviews. Molecular cell biology2022

Mechanism, cellular functions and cancer roles of polymerase-theta-mediated DNA end joining.

Dale A Ramsden, Juan Carvajal-Garcia, Gaorav P Gupta

Abstract readReview
In one paragraph

Review in Nature reviews. Molecular cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing 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

129 citing papers in PubMed.

  1. Review
  2. The Pharmacologic Profile of ART6043, a First-in-Class Clinical DNA Polymerase Theta Polymerase Domain Inhibitor Potentiating PARP Inhibitor Efficacy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  11. Article
  12. Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Gut microbes · 2025
    Article

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

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

3 authors.

Dale A RamsdenLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. dale_ramsden@med.unc.edu.ORCID http://orcid.org/0000-0003-1575-4748
Juan Carvajal-GarciaCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-7257-3674
Gaorav P GuptaLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. gaorav_gupta@med.unc.edu.

Funding

Structural determinants of Pol theta functionP01CA247773 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DALE A RAMSDEN · 2020 to 2026
$15.2M
NCI NIH HHS P01 CA247773
6 · The paper itself

Abstract

Cellular pathways that repair chromosomal double-strand breaks (DSBs) have pivotal roles in cell growth, development and cancer. These DSB repair pathways have been the target of intensive investigation, but one pathway - alternative end joining (a-EJ) - has long resisted elucidation. In this Review, we highlight recent progress in our understanding of a-EJ, especially the assignment of DNA polymerase theta (Polθ) as the predominant mediator of a-EJ in most eukaryotes, and discuss a potential molecular mechanism by which Polθ-mediated end joining (TMEJ) occurs. We address possible cellular functions of TMEJ in resolving DSBs that are refractory to repair by non-homologous end joining (NHEJ), DSBs generated following replication fork collapse and DSBs present owing to stalling of repair by homologous recombination. We also discuss how these context-dependent cellular roles explain how TMEJ can both protect against and cause genome instability, and the emerging potential of Polθ as a therapeutic target in cancer.

Indexed as

DNA End-Joining RepairAnimalsDNA-Directed DNA PolymeraseDNA Polymerase thetaDNA ReplicationHumansModels, BiologicalMutationNeoplasmsDNA-Directed DNA PolymeraseDNA Polymerase theta

Identifiers

PMID34522048
PMCPMC13537726

What Socratic holds

Textmetadata
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 Socratic graph.