Evidence map›Paper›PMID 19540301›Full record

ArticleBiochimie2009

High fidelity and lesion bypass capability of human DNA polymerase delta.

Michael W Schmitt, Yoshihiro Matsumoto, Lawrence A Loeb

Abstract read
In one paragraph

Article in Biochimie, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

71 citing papers in PubMed, 96 citations in OpenAlex.

  1. Review
  2. 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
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. DNA polymerase κ suppresses inflammation and inflammation-induced mutagenesis and carcinogenic potential in the colon of mice.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023
    Article
  11. Article
  12. Article
  13. Extrinsic proofreading.DNA repair · 2022
    Review
  14. Article
  15. Article
  16. How asymmetric DNA replication achieves symmetrical fidelity.Nature structural & molecular biology · 2021
    Article
  17. Article
  18. Article
  19. Article
  20. Visualizing Rev1 catalyze protein-template DNA synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article

11 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 at 2 institutions in 1 country.

Michael W SchmittDepartment of Biochemistry and Pathology, Joseph Gottstein Memorial Cancer Research Laboratory, University of Washington School of Medicine, Seattle, WA 98195, USA.
Yoshihiro Matsumoto
Lawrence A Loeb
Fox Chase Cancer Center · USUniversity of Washington · US

Funding

University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
Tumor mutation signaturesP01CA077852 · NCI · UNIVERSITY OF WASHINGTON · PI MAIZELS, NANCY · 1999 to 2019
$26.0M
Fidelity of DNA SynthesisR01CA102029 · NCI · UNIVERSITY OF WASHINGTON · PI LOEB, LAWRENCE A · 2003 to 2012
$3.3M
Mutator Phenotype in Human CancersR01CA115802 · NCI · UNIVERSITY OF WASHINGTON · PI LOEB, LAWRENCE A · 2007 to 2011
$1.5M
Mitochondrial DNA Replication FidelityF30AG030314 · NIA · UNIVERSITY OF WASHINGTON · PI SCHMITT, MICHAEL WILLIAM · 2007 to 2010
$132k
NCI NIH HHS P01 CA077852NCI NIH HHS R01 CA102029NCI NIH HHS R01 CA115802NIA NIH HHS F30 AG030314NIGMS NIH HHS T32 GM007266
6 · The paper itself

Abstract

DNA polymerase delta (Pol delta) is one of the main replicative DNA polymerases in human cells and therefore is a critical determinant of the overall accuracy of DNA synthesis. Here we document the fidelity of a human Pol delta holoenzyme and systematically score the types of mutations that the enzyme generates in a forward mutation assay. We find that human Pol delta is highly accurate, catalyzing less than one nucleotide mis-insertion per 220,000 nucleotides polymerized. Inactivation of proofreading or mutation of a conserved active site residue significantly elevates the frequency of incorporation errors, demonstrating the contribution of both the base selection and proofreading domains to the overall accuracy of synthesis by Pol delta. The highly selective nature of the polymerase active site is also indicated by the stalling of Pol delta upon encountering multiple types of DNA lesions. However, DNA damage is not an absolute block to Pol delta progression. We propose that partial lesion bypass by Pol delta represents a balance between stalling to allow for repair of mutagenic lesions by specialized repair proteins and bypass of damage to allow for successful completion of DNA synthesis by Pol delta in the presence of weakly blocking DNA adducts.

Indexed as

AnimalsBase SequenceCattleDNADNA Polymerase IIIDNA RepairDNA ReplicationElectrophoresis, Polyacrylamide GelFrameshift MutationHumansMolecular Sequence DataMutationSequence DeletionDNADNA Polymerase III

Identifiers

PMID19540301
PMCPMC2774493
OpenAlexW2091162590

What OpenQuestion holds

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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.