Evidence map›Paper›PMID 36840719›Full record

ArticleNucleic acids research2023

The mismatch repair endonuclease MutLα tethers duplex regions of DNA together and relieves DNA torsional tension.

Scott J Witte, Isabella M Rosa, Bryce W Collingwood, Jonathan M Piscitelli, Carol M Manhart

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

10 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  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. Review
  8. Review
  9. Article
  10. 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

5 authors at 1 institution in 1 country.

Scott J WitteDepartment of Chemistry, Temple University, Philadelphia, PA 19122, USA.
Isabella M RosaDepartment of Chemistry, Temple University, Philadelphia, PA 19122, USA.
Bryce W CollingwoodDepartment of Chemistry, Temple University, Philadelphia, PA 19122, USA.
Jonathan M PiscitelliDepartment of Chemistry, Temple University, Philadelphia, PA 19122, USA.
Carol M ManhartDepartment of Chemistry, Temple University, Philadelphia, PA 19122, USA.ORCID 0000-0002-0201-4348
Temple University · US

Funding

Molecular Mechanisms Of Modular Nuclease DomainsR35GM142651 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI MANHART, CAROL M · 2021 to 2025
$1.8M
NIGMS NIH HHS R35 GM142651
6 · The paper itself

Abstract

In eukaryotic mismatch repair, MutS homologs recognize mismatches and recruit the MutLα endonuclease which introduces a nick in the newly replicated, error-containing DNA strand. The nick occurs in response to the mismatch, but at a site up to several hundred base pairs away. The MutLα nick promotes mismatch excision by an exonuclease (Exo1) or removal by the strand displacement activity of a DNA polymerase which may work in conjunction with a flap endonuclease. Models have suggested that MutL homolog endonucleases form oligomeric complexes which facilitate and are activated by strand capture mechanisms, although such models have never been explicitly tested. We present evidence that the mismatch repair MutLα endonuclease is activated by DNA-DNA associations and that it can use this property to overcome DNA torsional barriers. Using DNA ligation and pull-down experiments, we determined that the MutLα endonuclease associates two DNA duplexes. Using nuclease assays, we determined that this activity stimulates MutLα's endonuclease function. We also observe that MutLα enhances a topoisomerase without nicking the DNA itself. Our data provide a mechanistic explanation for how MutL proteins interact with DNA during mismatch repair, and how MutL homologs participate in other processes, such as recombination and trinucleotide repeat expansions.

Indexed as

DNA Mismatch RepairEndonucleasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsDNADNA RepairMutL ProteinsDNAEndonucleasesMutL ProteinsSaccharomyces cerevisiae Proteins

Identifiers

PMID36840719
PMCPMC10085691
OpenAlexW4321996829

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.