Evidence map›Paper›PMID 24981171›Full record

ArticleMolecular cell2014

PCNA and Msh2-Msh6 activate an Mlh1-Pms1 endonuclease pathway required for Exo1-independent mismatch repair.

Eva M Goellner, Catherine E Smith, Christopher S Campbell, Hans Hombauer, Arshad Desai, Christopher D Putnam, Richard D Kolodner

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

79 citing papers in PubMed, 111 citations in OpenAlex.

  1. DNA Repair Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. Review
  3. Article
  4. DNA mismatch repair mediated by Mlh1-Pms1 endonuclease-catalyzed mispair excision.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. The mismatch repair factor Mlh1-Pms1 uses ATP to compact and remodel DNA.bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Effects of PCNA Stability on the Formation of Mutations.International journal of molecular sciences · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

19 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

7 authors at 2 institutions in 2 countries.

Eva M GoellnerLudwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA.
Catherine E SmithLudwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA.
Christopher S CampbellLudwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA.
Hans HombauerLudwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Arshad DesaiLudwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA.
Christopher D PutnamLudwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA.
Richard D KolodnerLudwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA; Moores-UCSD Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA; Institute of Genomic Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093-0669, USA. Electronic address: rkolodner@ucsd.edu.
University of California, San Diego · USLudwig Cancer Research · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
ENZYMOLOGY OF MISMATCH REPAIR IN YEASTR01GM050006 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Richard D Kolodner · 1994 to 2026
$10.5M
Kinetochore Specification and FunctionR01GM074215 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DESAI, ARSHAD · 2005 to 2025
$8.2M
Understanding the role of PCNA in DNA mismatch repair subpathwaysF32GM106598 · NIGMS · LUDWIG INSTITUTE FOR CANCER RES LTD · PI GOELLNER, EVA MARIE · 2013 to 2014
$102k
NCI NIH HHS CA23100NCI NIH HHS CA92584NCI NIH HHS P01 CA092584NCI NIH HHS P30 CA023100NIGMS NIH HHS F32 GM106598NIGMS NIH HHS F32GM106598NIGMS NIH HHS GM074215NIGMS NIH HHS GM50006NIGMS NIH HHS R01 GM050006NIGMS NIH HHS R01 GM074215
6 · The paper itself

Abstract

Genetic evidence has implicated multiple pathways in eukaryotic DNA mismatch repair (MMR) downstream of mispair recognition and Mlh1-Pms1 recruitment, including Exonuclease 1 (Exo1)-dependent and -independent pathways. We identified 14 mutations in POL30, which encodes PCNA in Saccharomyces cerevisiae, specific to Exo1-independent MMR. The mutations identified affected amino acids at three distinct sites on the PCNA structure. Multiple mutant PCNA proteins had defects either in trimerization and Msh2-Msh6 binding or in activation of the Mlh1-Pms1 endonuclease that initiates excision during MMR. The latter class of mutations led to hyperaccumulation of repair intermediate Mlh1-Pms1 foci and were enhanced by an msh6 mutation that disrupted the Msh2-Msh6 interaction with PCNA. These results reveal a central role for PCNA in the Exo1-independent MMR pathway and suggest that Msh2-Msh6 localizes PCNA to repair sites after mispair recognition to activate the Mlh1-Pms1 endonuclease for initiating Exo1-dependent repair or for driving progressive excision in Exo1-independent repair.

Indexed as

Adaptor Proteins, Signal TransducingCarrier ProteinsDNA-Binding ProteinsDNA, FungalDNA Mismatch RepairEnzyme ActivationExodeoxyribonucleasesModels, MolecularMutation, MissenseMutL Protein Homolog 1MutL ProteinsMutS Homolog 2 ProteinProliferating Cell Nuclear AntigenProtein BindingProtein Interaction Domains and MotifsProtein MultimerizationAdaptor Proteins, Signal TransducingCarrier ProteinsDNA-Binding ProteinsDNA, Fungalexodeoxyribonuclease IExodeoxyribonucleasesMLH1 protein, S cerevisiaeMSH2 protein, S cerevisiaeMSH6 protein, S cerevisiaeMutL Protein Homolog 1MutL ProteinsMutS Homolog 2 ProteinPMS1 protein, S cerevisiaePOL30 protein, S cerevisiaeProliferating Cell Nuclear AntigenSaccharomyces cerevisiae Proteins

Identifiers

PMID24981171
PMCPMC4113420
OpenAlexW2058951716

What OpenQuestion holds

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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.