Evidence map›Paper›PMID 33577776›Full record

ArticleMolecular cell2021

RETRACTED: Human DNA polymerase θ harbors DNA end-trimming activity critical for DNA repair.

Karl E Zahn, Ryan B Jensen, Richard D Wood, Sylvie Doublié

RetractedOpen access · bronzeAbstract readRetracted Publication
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. It has been retracted, and should not be counted. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Role of Alkali Cations in DNA-Thioflavin T Interaction.The journal of physical chemistry. B · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Multifaceted Nature of DNA Polymerase θ.International journal of molecular sciences · 2023
    Review
  9. Article
  10. Genome Protection by DNA Polymerase θ.Annual review of genetics · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Karl E ZahnDepartment of Microbiology and Molecular Genetics, University of Vermont, 89 Beaumont Ave., Burlington, VT 05405, USA; Department of Therapeutic Radiology, Yale University, New Haven, CT 06510, USA.
Ryan B JensenDepartment of Therapeutic Radiology, Yale University, New Haven, CT 06510, USA.
Richard D WoodDepartment of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 78957, USA. Electronic address: rwood@mdanderson.org.
Sylvie DoubliéDepartment of Microbiology and Molecular Genetics, University of Vermont, 89 Beaumont Ave., Burlington, VT 05405, USA. Electronic address: sdoublie@uvm.edu.
Yale University · US

Funding

Structural determinants of Pol theta functionP01CA247773 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Gaorav P. Gupta · 2020 to 2026
$15.2M
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
Processing of Radiation Damage by Translesion DNA SynthesisR01CA052040 · NCI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI DOUBLIE, SYLVIE · 1991 to 2017
$4.5M
Elucidating Cancer Risk in BRCA2 and RAD51 VariantsR01CA215990 · NCI · YALE UNIVERSITY · PI JENSEN, RYAN BROWN · 2017 to 2021
$1.9M
Howard Hughes Medical InstituteNCI NIH HHS P01 CA193124NCI NIH HHS P01 CA247773NCI NIH HHS R01 CA052040NCI NIH HHS R01 CA215990
6 · The paper itself

Abstract

Cancers with hereditary defects in homologous recombination rely on DNA polymerase θ (pol θ) for repair of DNA double-strand breaks. During end joining, pol θ aligns microhomology tracts internal to 5'-resected broken ends. An unidentified nuclease trims the 3' ends before synthesis can occur. Here we report that a nuclease activity, which differs from the proofreading activity often associated with DNA polymerases, is intrinsic to the polymerase domain of pol θ. Like the DNA synthesis activity, the nuclease activity requires conserved metal-binding residues, metal ions, and dNTPs and is inhibited by ddNTPs or chain-terminated DNA. Our data indicate that pol θ repurposes metal ions in the polymerase active site for endonucleolytic cleavage and that the polymerase-active and end-trimming conformations of the enzyme are distinct. We reveal a nimble strategy of substrate processing that allows pol θ to trim or extend DNA depending on the DNA repair context.

Indexed as

DNA Breaks, Double-StrandedDNA RepairCell LineDNADNA-Directed DNA PolymeraseDNA Polymerase thetaEndonucleasesHumansMetalsDNADNA-Directed DNA PolymeraseDNA Polymerase thetaEndonucleasesMetalsdideoxynucleotidesDNA polymeraseDouble-strand break repairendonucleasetheta-mediated end joining (TMEJ)

Identifiers

PMID33577776
PMCPMC8231307
OpenAlexW3127149415

What OpenQuestion holds

Textmetadata
LicenceTDM
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.