Evidence map›Paper›PMID 22659005›Full record

ArticleJournal of molecular biology2012

The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair.

Aaron J Plys, Maria V Rogacheva, Eric C Greene, Eric Alani

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

30 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. The mismatch repair factor Mlh1-Pms1 uses ATP to compact and remodel DNA.bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. 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
  13. Article
  14. Article
  15. 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
  16. Article
  17. Review
  18. Article
  19. Article
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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

4 authors at 2 institutions in 1 country.

Aaron J PlysDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2073, USA.
Maria V Rogacheva
Eric C Greene
Eric Alani
Cornell University · USColumbia University · US

Funding

Roles for Mismatch Repair Proteins in Maintaining Genome StabilityR01GM053085 · NIGMS · CORNELL UNIVERSITY ITHACA · PI ALANI, ERIC E. · 1995 to 2019
$7.3M
Visualizing the Dynamics of Chromatin and Chromatin Remodeling ProteinsR01GM082848 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GREENE, ERIC C · 2008 to 2016
$2.4M
Howard Hughes Medical InstituteNIGMS NIH HHS GM053085NIGMS NIH HHS GM082848NIGMS NIH HHS R01 GM053085NIGMS NIH HHS R01 GM082848
6 · The paper itself

Abstract

DNA mismatch repair (MMR) models have proposed that MSH (MutS homolog) proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH (MutL homolog) proteins (primarily Mlh1-Pms1 in baker's yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20-30 nm) unstructured arms that connect two terminal globular domains. These arms can vary between 100 and 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker's yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR.

Indexed as

Adaptor Proteins, Signal TransducingBase Pair MismatchBinding SitesCarrier ProteinsDNA-Binding ProteinsDNA, FungalDNA Mismatch RepairGenome, FungalMutL Protein Homolog 1MutL ProteinsMutS Homolog 2 ProteinProtein ConformationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAdaptor Proteins, Signal TransducingCarrier ProteinsDNA-Binding ProteinsDNA, FungalMLH1 protein, S cerevisiaeMSH2 protein, S cerevisiaeMSH6 protein, S cerevisiaeMutL Protein Homolog 1MutL ProteinsMutS Homolog 2 ProteinPMS1 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID22659005
PMCPMC3418407
OpenAlexW2033639747

What OpenQuestion holds

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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.