Evidence map›Paper›PMID 19022408›Full record

ArticleDNA repair2009

Human MutL-complexes monitor homologous recombination independently of mismatch repair.

Simone Yasmin Siehler, Michael Schrauder, Ulrike Gerischer, Sharon Cantor, Giancarlo Marra, Lisa Wiesmüller

Abstract read
In one paragraph

Article in DNA repair, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. DNA Damage Repair in Huntington's Disease and Other Neurodegenerative Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019
    Review
  3. Journal of Cancer · 2018
    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

6 authors at 4 institutions in 3 countries.

Simone Yasmin SiehlerUniversitatsfrauenklinik, Prittwitzstrasse 43, D-89075 Ulm, Germany.
Michael Schrauder
Ulrike Gerischer
Sharon Cantor
Giancarlo Marra
Lisa Wiesmüller
Universitäts Frauenklinik · DEUniversität Ulm · DEUniversity of Massachusetts Chan Medical School · USUniversity of Zurich · CH

Funding

BACH1/FANCJ Checkpoint, Recombination, and ChemoresistanceR01CA129514 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CANTOR, SHARON B · 2007 to 2011
$1.6M
NCI NIH HHS R01 CA129514
6 · The paper itself

Abstract

The role of mismatch repair proteins has been well studied in the context of DNA repair following DNA polymerase errors. Particularly in yeast, MSH2 and MSH6 have also been implicated in the regulation of genetic recombination, whereas MutL homologs appeared to be less important. So far, little is known about the role of the human MutL homolog hMLH1 in recombination, but recently described molecular interactions suggest an involvement. To identify activities of hMLH1 in this process, we applied an EGFP-based assay for the analysis of different mechanisms of DNA repair, initiated by a targeted double-stranded DNA break. We analysed 12 human cellular systems, differing in the hMLH1 and concomitantly in the hPMS1 and hPMS2 status via inducible protein expression, genetic reconstitution, or RNA interference. We demonstrate that hMLH1 and its complex partners hPMS1 and hPMS2 downregulate conservative homologous recombination (HR), particularly when involving DNA sequences with only short stretches of uninterrupted homology. Unexpectedly, hMSH2 is dispensable for this effect. Moreover, the damage-signaling kinase ATM and its substrates BLM and BACH1 are not strictly required, but the combined effect of ATM/ATR-signaling components may mediate the anti-recombinogenic effect. Our data indicate a protective role of hMutL-complexes in a process which may lead to detrimental genome rearrangements, in a manner which does not depend on mismatch repair.

Indexed as

DNA Mismatch RepairRecombination, GeneticAdaptor Proteins, Signal TransducingAdenosine TriphosphatasesAtaxia Telangiectasia Mutated ProteinsBasic-Leucine Zipper Transcription FactorsCell Cycle ProteinsCell Line, TumorChromosomes, HumanDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA Repair EnzymesFanconi Anemia Complementation Group ProteinsHumansMismatch Repair Endonuclease PMS2Multiprotein ComplexesAdaptor Proteins, Signal TransducingAdenosine TriphosphatasesAtaxia Telangiectasia Mutated ProteinsATM protein, humanBACH1 protein, humanBasic-Leucine Zipper Transcription FactorsBloom syndrome proteinCell Cycle ProteinsDNA-Binding ProteinsDNA Repair EnzymesFanconi Anemia Complementation Group ProteinsMismatch Repair Endonuclease PMS2MLH1 protein, humanMSH2 protein, humanMultiprotein ComplexesMutL Protein Homolog 1MutL ProteinsMutS Homolog 2 ProteinNeoplasm ProteinsNuclear ProteinsPMS1 protein, humanPMS2 protein, humanProtein Serine-Threonine KinasesRecQ HelicasesTumor Suppressor Proteins

Identifiers

PMID19022408
PMCPMC2909591
OpenAlexW2090116556

What OpenQuestion holds

Textmetadata
LicenceTDM
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.