Evidence map›Paper›PMID 40049731›Full record

ArticleLife science alliance2025

MDC1 mediates Pellino recruitment to sites of DNA double-strand breaks.

Mònica Torres Esteban, Matthew J Stewart, Eilis Bragginton, Alice Meroni, Annica Pellizzari, Alain Jeanrenaud, Stephen J Smerdon, Manuel Stucki

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Life science alliance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Mònica Torres Estebanhttps://ror.org/02crff812 Department of Gynecology, University of Zurich and University Hospital of Zurichhttps://ror.org/01462r250 , Schlieren, Switzerland.
Matthew J Stewarthttps://ror.org/03angcq70 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Eilis Braggintonhttps://ror.org/03angcq70 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.ORCID 0000-0003-0256-6537
Alice Meronihttps://ror.org/02crff812 Department of Gynecology, University of Zurich and University Hospital of Zurichhttps://ror.org/01462r250 , Schlieren, Switzerland.ORCID 0000-0003-3568-8207
Annica Pellizzarihttps://ror.org/02crff812 Department of Gynecology, University of Zurich and University Hospital of Zurichhttps://ror.org/01462r250 , Schlieren, Switzerland.
Alain Jeanrenaudhttps://ror.org/02crff812 Department of Gynecology, University of Zurich and University Hospital of Zurichhttps://ror.org/01462r250 , Schlieren, Switzerland.
Stephen J Smerdonhttps://ror.org/03angcq70 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK s.j.smerdon@bham.ac.uk.ORCID 0000-0001-5688-8465
Manuel Stuckihttps://ror.org/02crff812 Department of Gynecology, University of Zurich and University Hospital of Zurichhttps://ror.org/01462r250 , Schlieren, Switzerland manuel.stucki@uzh.ch.ORCID 0000-0002-9974-0134

Funding

Biotechnology and Biological Sciences Research Council (BBSRC) and University of Birmingham MIBTP) BB/T00746X/1Cancer Research UK FC001003Medical Research Council FC001003Wellcome Trust FC001003
6 · The paper itself

Abstract

Ubiquitylation is critically implicated in the recognition and repair of DNA double-strand breaks. The adaptor protein MDC1 mediates the recruitment of the key DNA damage responsive E3 ubiquitin ligase RNF8 to the break sites. It does so by directly interacting with RNF8 in a phosphorylation-dependent manner that involves the RNF8 FHA domain, thus initiating targeted chromatin ubiquitylation at the break sites. Here, we report that MDC1 also directly binds to two additional E3 ubiquitin ligases, Pellino 1 and 2, which were recently implicated in the DNA damage response. Through a combination of biochemical, biophysical and X-ray crystallographic approaches, we reveal the molecular details of the MDC1-Pellino complexes. Furthermore, we show that in mammalian cells, MDC1 mediates Pellino recruitment to sites of DNA double-strand breaks by a direct phosphorylation-dependent interaction between the two proteins. Taken together, our findings provide new molecular insights into the ubiquitylation pathways that govern genome stability maintenance.

Indexed as

Cell Cycle ProteinsDNA Breaks, Double-StrandedNuclear ProteinsTrans-ActivatorsUbiquitin-Protein LigasesAdaptor Proteins, Signal TransducingCrystallography, X-RayDNA-Binding ProteinsDNA RepairHEK293 CellsHumansPhosphorylationProtein BindingUbiquitinationAdaptor Proteins, Signal TransducingCell Cycle ProteinsDNA-Binding ProteinsMDC1 protein, humanNuclear ProteinsRNF8 protein, humanTrans-ActivatorsUbiquitin-Protein Ligases

Identifiers

PMID40049731
PMCPMC11884936

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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.