Evidence map›Paper›PMID 33619096›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Linker domain function predicts pathogenic MLH1 missense variants.

James London, Juana Martín-López, Inho Yang, Jiaquan Liu, Jong-Bong Lee, Richard Fishel

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.1field-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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. 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
  4. Article
  5. 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
  6. Article
  7. 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
  8. Article
  9. Review
  10. Review
  11. 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

6 authors at 2 institutions in 2 countries.

James LondonDepartment of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210.ORCID 0000-0003-2638-0868
Juana Martín-LópezDepartment of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210.ORCID 0000-0003-2777-2740
Inho YangDepartment of Physics, Pohang University of Science and Technology, Pohang, Korea 37673.ORCID 0000-0001-6830-7357
Jiaquan LiuDepartment of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210.
Jong-Bong LeeDepartment of Physics, Pohang University of Science and Technology, Pohang, Korea 37673; rfishel@osu.edu jblee@postech.ac.kr.ORCID 0000-0003-2235-1912
Richard FishelDepartment of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210; rfishel@osu.edu jblee@postech.ac.kr.
The Ohio State University Wexner Medical Center · USPohang University of Science and Technology · KR

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
The Human Mismatch Repair Proteins and CarcinogenesisR01CA067007 · NCI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI Richard Fishel · 1995 to 2026
$9.6M
NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA067007
6 · The paper itself

Abstract

The pathogenic consequences of 369 unique human HsMLH1 missense variants has been hampered by the lack of a detailed function in mismatch repair (MMR). Here single-molecule images show that HsMSH2-HsMSH6 provides a platform for HsMLH1-HsPMS2 to form a stable sliding clamp on mismatched DNA. The mechanics of sliding clamp progression solves a significant operational puzzle in MMR and provides explicit predictions for the distribution of clinically relevant HsMLH1 missense mutations.

Indexed as

DNA Mismatch RepairMutation, MissenseBinding SitesColorectal Neoplasms, Hereditary NonpolyposisDNADNA-Binding ProteinsDNA DamageHumansModels, MolecularMutL Protein Homolog 1MutS Homolog 2 ProteinProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsDNADNA-Binding ProteinsG-T mismatch-binding proteinMLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinHNPCCLynch syndromemismatch repairsingle moleculesliding clamp

Identifiers

PMID33619096
PMCPMC7936337
OpenAlexW3131776487

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.