Evidence map›Paper›PMID 21931565›Full record

ArticlePLoS genetics2011

Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks.

Petra Langerak, Eva Mejia-Ramirez, Oliver Limbo, Paul Russell

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

161 citing papers in PubMed, 223 citations in OpenAlex.

  1. Mechanisms and disease relevance of DNA break repair pathway choice.Nature reviews. Molecular cell biology · 2026
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  10. MRE11A: a novel negative regulator of human DNA mismatch repair.Cellular & molecular biology letters · 2024
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101 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Petra LangerakDepartment of Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Eva Mejia-Ramirez
Oliver Limbo
Paul Russell
Scripps Research Institute · US

Funding

Studies of the DNA damage checkpointsR01CA077325 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI RUSSELL, PAUL · 1998 to 2017
$7.1M
NCI NIH HHS CA77325NCI NIH HHS R01 CA077325
6 · The paper itself

Abstract

The multifunctional Mre11-Rad50-Nbs1 (MRN) protein complex recruits ATM/Tel1 checkpoint kinase and CtIP/Ctp1 homologous recombination (HR) repair factor to double-strand breaks (DSBs). HR repair commences with the 5'-to-3' resection of DNA ends, generating 3' single-strand DNA (ssDNA) overhangs that bind Replication Protein A (RPA) complex, followed by Rad51 recombinase. In Saccharomyces cerevisiae, the Mre11-Rad50-Xrs2 (MRX) complex is critical for DSB resection, although the enigmatic ssDNA endonuclease activity of Mre11 and the DNA-end processing factor Sae2 (CtIP/Ctp1 ortholog) are largely unnecessary unless the resection activities of Exo1 and Sgs1-Dna2 are also eliminated. Mre11 nuclease activity and Ctp1/CtIP are essential for DSB repair in Schizosaccharomyces pombe and mammals. To investigate DNA end resection in Schizo. pombe, we adapted an assay that directly measures ssDNA formation at a defined DSB. We found that Mre11 and Ctp1 are essential for the efficient initiation of resection, consistent with their equally crucial roles in DSB repair. Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1) DNA helicase having a minor role. Despite its critical function in DSB repair, Mre11 nuclease activity is not required for resection in fission yeast. However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ) complex from DSBs, which is required for efficient RPA localization. Eliminating Ku makes Mre11 nuclease activity dispensable for MRN disassociation and RPA localization, while improving repair of a one-ended DSB formed by replication fork collapse. From these data we propose that release of the MRN complex and Ku from DNA ends by Mre11 nuclease activity and Ctp1 is a critical step required to expose ssDNA for RPA localization and ensuing HR repair.

Indexed as

Chromosomal Proteins, Non-HistoneDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA End-Joining RepairDNA HelicasesDNA RepairDNA, Single-StrandedExodeoxyribonucleasesHomologous RecombinationMultiprotein ComplexesRad51 RecombinaseReplication Protein ASchizosaccharomycesSchizosaccharomyces pombe ProteinsChromosomal Proteins, Non-HistoneCtp1 protein, S pombeDNA-Binding ProteinsDNA HelicasesDNA, Single-Strandedexodeoxyribonuclease IExodeoxyribonucleasesMultiprotein ComplexesNbs1 protein, S pombeRad50 protein, S pombeRad51 RecombinaseReplication Protein ARqh1 protein, S pombeSchizosaccharomyces pombe Proteins

Identifiers

PMID21931565
PMCPMC3169521
OpenAlexW2011419995

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.