Evidence map›Paper›PMID 21113133›Full record

ArticleThe EMBO journal2010

RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells.

Wojciech Piwko, Michael H Olma, Michael Held, Julien N Bianco, Patrick G A Pedrioli, Kay Hofmann, Philippe Pasero, Daniel W Gerlich, Matthias Peter

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

50 citing papers in PubMed, 75 citations in OpenAlex.

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  20. Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia.American journal of human genetics · 2019
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Wojciech PiwkoInstitute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland. wojciech.piwko@bc.biol.ethz.ch
Michael H Olma
Michael Held
Julien N Bianco
Patrick G A Pedrioli
Kay Hofmann
Philippe Pasero
Daniel W Gerlich
Matthias Peter
ETH Zurich · CHCentre National de la Recherche Scientifique · FRInstitut de Génétique Humaine · FRMiltenyi Biotec (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cullin 4 (Cul4)-based ubiquitin ligases emerged as critical regulators of DNA replication and repair. Over 50 Cul4-specific adaptors (DNA damage-binding 1 (Ddb1)-Cul4-associated factors; DCAFs) have been identified and are thought to assemble functionally distinct Cul4 complexes. Using a live-cell imaging-based RNAi screen, we analysed the function of DCAFs and Cul4-linked proteins, and identified specific subsets required for progression through G1 and S phase. We discovered C6orf167/Mms22-like protein (Mms22L) as a putative human orthologue of budding yeast Mms22, which, together with cullin Rtt101, regulates genome stability by promoting DNA replication through natural pause sites and damaged templates. Loss of Mms22L function in human cells results in S phase-dependent genomic instability characterised by spontaneous double-strand breaks and DNA damage checkpoint activation. Unlike yeast Mms22, human Mms22L does not stably bind to Cul4, but is degraded in a Cul4-dependent manner and upon replication stress. Mms22L physically and functionally interacts with the scaffold-like protein Nfkbil2 that co-purifies with histones, several chromatin remodelling and DNA replication/repair factors. Together, our results strongly suggest that the Mms22L-Nfkbil2 complex contributes to genome stability by regulating the chromatin state at stalled replication forks.

Indexed as

DNA ReplicationCell Line, TumorDNA-Binding ProteinsGene Knockdown TechniquesGenomic InstabilityHumansMass ScreeningNF-kappa BNuclear ProteinsRNA, Small InterferingDNA-Binding ProteinsMMS22L protein, humanNF-kappa BNuclear ProteinsRNA, Small InterferingTONSL protein, human

Identifiers

PMID21113133
PMCPMC3018799
OpenAlexW2012312296

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.