Evidence map›Paper›PMID 18854319›Full record

ArticleThe Journal of biological chemistry2008

Mechanism of MutS searching for DNA mismatches and signaling repair.

Ingrid Tessmer, Yong Yang, Jie Zhai, Chungwei Du, Peggy Hsieh, Manju M Hingorani, Dorothy A Erie

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
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

40 citing papers in PubMed.

  1. Article
  2. Article
  3. Nucleic Acids and Electrical Signals.Reviews of physiology, biochemistry and pharmacology · 2025
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. The methylation-independent mismatch repair machinery inMicrobiology (Reading, England) · 2021
    Review
  9. Article
  10. Review
  11. The selection process of licensing a DNA mismatch for repair.Nature structural & molecular biology · 2021
    Article
  12. Article
  13. Mismatch Recognition byInternational journal of molecular sciences · 2019
    Article
  14. Article
  15. Studying protein-DNA interactions using atomic force microscopy.Seminars in cell & developmental biology · 2018
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

7 authors.

Ingrid TessmerDepartment of Chemistry and Curriculum in Applied Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Yong Yang
Jie Zhai
Chungwei Du
Peggy Hsieh
Manju M Hingorani
Dorothy A Erie

Funding

DNA Mismatch RepairZIADK052030 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI HSIEH, PEGGY · 2009 to 2014
$3.6M
Structure Function Studies of DNA Mismatch RepairR01GM079480 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ERIE, DOROTHY A · 2007 to 2017
$2.7M
DOCTORAL STUDIES IN MOLECULAR BIOPHYSICST32GM008271 · NIGMS · WESLEYAN UNIVERSITY · PI BEVERIDGE, DAVID LEWIS · 1988 to 2015
$1.8M
Mechanistic studies of DNA repair and damage responseR01GM080294 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ERIE, DOROTHY A · 2009 to 2010
$565k
Intramural NIH HHSNIGMS NIH HHS GM079480NIGMS NIH HHS R01 GM079480NIGMS NIH HHS R01 GM080294NIGMS NIH HHS T32 GM008271
6 · The paper itself

Abstract

DNA mismatch repair is initiated by the recognition of mismatches by MutS proteins. The mechanism by which MutS searches for and recognizes mismatches and subsequently signals repair remains poorly understood. We used single-molecule analyses of atomic force microscopy images of MutS-DNA complexes, coupled with biochemical assays, to determine the distributions of conformational states, the DNA binding affinities, and the ATPase activities of wild type and two mutants of MutS, with alanine substitutions in the conserved Phe-Xaa-Glu mismatch recognition motif. We find that on homoduplex DNA, the conserved Glu, but not the Phe, facilitates MutS-induced DNA bending, whereas at mismatches, both Phe and Glu promote the formation of an unbent conformation. The data reveal an unusual role for the Phe residue in that it promotes the unbending, not bending, of DNA at mismatch sites. In addition, formation of the specific unbent MutS-DNA conformation at mismatches appears to be required for the inhibition of ATP hydrolysis by MutS that signals initiation of repair. These results provide a structural explanation for the mechanism by which MutS searches for and recognizes mismatches and for the observed phenotypes of mutants with substitutions in the Phe-Xaa-Glu motif.

Indexed as

Base Pair MismatchDNA RepairAdenosine TriphosphateAmino Acid MotifsBase SequenceDNAHydrolysisMicroscopy, Atomic ForceModels, BiologicalModels, GeneticMolecular Sequence DataMutS DNA Mismatch-Binding ProteinPhenotypeProtein ConformationThermusAdenosine TriphosphateDNAMutS DNA Mismatch-Binding Protein

Identifiers

PMID18854319
PMCPMC2606009

What OpenQuestion holds

Textmetadata
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.