Evidence map›Paper›PMID 31598722›Full record

ArticleNucleic acids research2019

The unstructured linker arms of MutL enable GATC site incision beyond roadblocks during initiation of DNA mismatch repair.

Yannicka S N Mardenborough, Katerina Nitsenko, Charlie Laffeber, Camille Duboc, Enes Sahin, Audrey Quessada-Vial, Herrie H K Winterwerp, Titia K Sixma, Roland Kanaar, Peter Friedhoff and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.0field-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

23 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. How Genomic and Structural Context Could Shape JAK-STAT Variant Pathogenicity.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026
    Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Insights into DNA cleavage by MutL homologs from analysis of conserved motifs in eukaryotic Mlh1.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Article
  9. Article
  10. Review
  11. The unstructured linker of Mlh1 contains a motif required for endonuclease function which is mutated in cancers.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Linker domain function predicts pathogenic MLH1 missense variants.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  18. Review
  19. Review
  20. MutS sliding clamps on an uncertain track to DNA mismatch repair.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
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

12 authors at 4 institutions in 3 countries.

Yannicka S N MardenboroughDepartment of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.
Katerina NitsenkoInstitut Jacques Monod, CNRS, UMR7592, University Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
Charlie LaffeberDepartment of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.
Camille DubocInstitut Jacques Monod, CNRS, UMR7592, University Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
Enes SahinDepartment of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.
Audrey Quessada-VialInstitut Jacques Monod, CNRS, UMR7592, University Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
Herrie H K WinterwerpDivision of Biochemistry, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Titia K SixmaOncode Institute, the Netherlands.
Roland KanaarDepartment of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.
Peter FriedhoffInstitute for Biochemistry, Justus-Liebig University, Giessen, Germany.
Terence R StrickInstitut Jacques Monod, CNRS, UMR7592, University Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
Joyce H G LebbinkDepartment of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.
Erasmus MC · NLCentre National de la Recherche Scientifique · FRThe Netherlands Cancer Institute · NLJustus-Liebig-Universität Gießen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA mismatch repair (MMR) maintains genome stability through repair of DNA replication errors. In Escherichia coli, initiation of MMR involves recognition of the mismatch by MutS, recruitment of MutL, activation of endonuclease MutH and DNA strand incision at a hemimethylated GATC site. Here, we studied the mechanism of communication that couples mismatch recognition to daughter strand incision. We investigated the effect of catalytically-deficient Cas9 as well as stalled RNA polymerase as roadblocks placed on DNA in between the mismatch and GATC site in ensemble and single molecule nanomanipulation incision assays. The MMR proteins were observed to incise GATC sites beyond a roadblock, albeit with reduced efficiency. This residual incision is completely abolished upon shortening the disordered linker regions of MutL. These results indicate that roadblock bypass can be fully attributed to the long, disordered linker regions in MutL and establish that communication during MMR initiation occurs along the DNA backbone.

Indexed as

Base Pair MismatchCRISPR-Associated Protein 9Deoxyribonucleases, Type II Site-SpecificDNA, BacterialDNA-Binding ProteinsDNA-Directed RNA PolymerasesDNA Mismatch RepairDNA Repair EnzymesEndodeoxyribonucleasesEscherichia coliEscherichia coli ProteinsGenomic InstabilityMutL ProteinsMutS DNA Mismatch-Binding ProteinCRISPR-Associated Protein 9Deoxyribonucleases, Type II Site-SpecificDNA, BacterialDNA-Binding ProteinsDNA-Directed RNA PolymerasesDNA Repair EnzymesEndodeoxyribonucleasesEscherichia coli ProteinsGATC-specific type II deoxyribonucleasesmethyl-directed mismatch repair protein, E coliMutL protein, E coliMutL ProteinsMutS DNA Mismatch-Binding ProteinMutS protein, E coli

Identifiers

PMID31598722
PMCPMC6902014
OpenAlexW2980194015

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.