Evidence map›Paper›PMID 29127375›Full record

ArticleScientific reports2017

DNA damage-induced histone H1 ubiquitylation is mediated by HUWE1 and stimulates the RNF8-RNF168 pathway.

I K Mandemaker, L van Cuijk, R C Janssens, H Lans, K Bezstarosti, J H Hoeijmakers, J A Demmers, W Vermeulen, J A Marteijn

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
2.7field-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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

I K MandemakerDepartment of Molecular Genetics, Oncode Institute, Cancer Genomics Netherlands, Erasmus Medical Centre, Rotterdam, The Netherlands.
L van CuijkDepartment of Molecular Genetics, Oncode Institute, Cancer Genomics Netherlands, Erasmus Medical Centre, Rotterdam, The Netherlands.
R C JanssensDepartment of Molecular Genetics, Oncode Institute, Cancer Genomics Netherlands, Erasmus Medical Centre, Rotterdam, The Netherlands.
H LansDepartment of Molecular Genetics, Oncode Institute, Cancer Genomics Netherlands, Erasmus Medical Centre, Rotterdam, The Netherlands.ORCID 0000-0003-4417-5358
K BezstarostiDepartment of Proteomics, Erasmus Medical Centre, Rotterdam, The Netherlands.
J H HoeijmakersDepartment of Molecular Genetics, Oncode Institute, Cancer Genomics Netherlands, Erasmus Medical Centre, Rotterdam, The Netherlands.
J A DemmersDepartment of Proteomics, Erasmus Medical Centre, Rotterdam, The Netherlands.
W VermeulenDepartment of Molecular Genetics, Oncode Institute, Cancer Genomics Netherlands, Erasmus Medical Centre, Rotterdam, The Netherlands.
J A MarteijnDepartment of Molecular Genetics, Oncode Institute, Cancer Genomics Netherlands, Erasmus Medical Centre, Rotterdam, The Netherlands. J.Marteijn@erasmusmc.nl.
Oncode Institute · NLErasmus University Rotterdam · NL

Funding

European Research Council 340988
6 · The paper itself

Abstract

The DNA damage response (DDR), comprising distinct repair and signalling pathways, safeguards genomic integrity. Protein ubiquitylation is an important regulatory mechanism of the DDR. To study its role in the UV-induced DDR, we characterized changes in protein ubiquitylation following DNA damage using quantitative di-Gly proteomics. Interestingly, we identified multiple sites of histone H1 that are ubiquitylated upon UV-damage. We show that UV-dependent histone H1 ubiquitylation at multiple lysines is mediated by the E3-ligase HUWE1. Recently, it was shown that poly-ubiquitylated histone H1 is an important signalling intermediate in the double strand break response. This poly-ubiquitylation is dependent on RNF8 and Ubc13 which extend pre-existing ubiquitin modifications to K63-linked chains. Here we demonstrate that HUWE1 depleted cells showed reduced recruitment of RNF168 and 53BP1 to sites of DNA damage, two factors downstream of RNF8 mediated histone H1 poly-ubiquitylation, while recruitment of MDC1, which act upstream of histone H1 ubiquitylation, was not affected. Our data show that histone H1 is a prominent target for ubiquitylation after UV-induced DNA damage. Our data are in line with a model in which HUWE1 primes histone H1 with ubiquitin to allow ubiquitin chain elongation by RNF8, thereby stimulating the RNF8-RNF168 mediated DDR.

Indexed as

DNA DamageUbiquitinationUltraviolet RaysDNA-Binding ProteinsHeLa CellsHistonesHumansSignal TransductionTumor Suppressor ProteinsUbiquitin-Protein LigasesDNA-Binding ProteinsHistonesHUWE1 protein, humanRNF168 protein, humanRNF8 protein, humanTumor Suppressor ProteinsUbiquitin-Protein Ligases

Identifiers

PMID29127375
PMCPMC5681673
OpenAlexW2767479705

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.