Evidence map›Paper›PMID 41145912›Full record

ArticleThe EMBO journal2025

H2BK120ub and its reader RNF169 sequentially regulate replication fork remodeling and stability.

Filip D Duzanic, Vaishnavi Mohana-Natarajan, Samuele Fisicaro, Collin Bakker, Moses Aouami, Gabriel Amaral, Massimo Lopes, Nitika Taneja, Lorenza Penengo

Abstract read
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In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

  1. Review
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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.

Filip D Duzanic *University of Zurich, Institute of Molecular Cancer Research, 8057, Zurich, Switzerland.
Vaishnavi Mohana-Natarajan *University of Zurich, Institute of Molecular Cancer Research, 8057, Zurich, Switzerland.
Samuele FisicaroUniversity of Zurich, Institute of Molecular Cancer Research, 8057, Zurich, Switzerland.ORCID http://orcid.org/0009-0000-2880-0147
Collin BakkerDepartment of Molecular Genetics, Erasmus University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.ORCID http://orcid.org/0009-0005-1322-9650
Moses AouamiUniversity of Zurich, Institute of Molecular Cancer Research, 8057, Zurich, Switzerland.
Gabriel AmaralUniversity of Zurich, Institute of Molecular Cancer Research, 8057, Zurich, Switzerland.ORCID http://orcid.org/0009-0008-8293-3491
Massimo LopesUniversity of Zurich, Institute of Molecular Cancer Research, 8057, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-3847-8133
Nitika TanejaDepartment of Molecular Genetics, Erasmus University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-5513-5282
Lorenza PenengoUniversity of Zurich, Institute of Molecular Cancer Research, 8057, Zurich, Switzerland. penengo@imcr.uzh.ch.ORCID http://orcid.org/0000-0001-7888-4473

Funding

EC | European Research Council (ERC) 10107875Krebsliga Schweiz (Swiss Cancer League) KFS- 4577-08-2018NWO-Vidi funding 114122Oncode Institute 115886Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF) 310030_184966/1Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF) 310030_219393Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF) 310030_220022/1Worldwide Cancer Research (WCR) 22-0181
6 · The paper itself

Abstract

Ubiquitination of the C-terminus of histone H2B (H2BK120ub) is a key histone modification with functions in a wide array of DNA-related processes, best characterized in gene transcription and repair. A role for H2B ubiquitination in DNA replication has been postulated and investigated in yeast but is still elusive in human cells. Here, we uncovered a critical function of H2BK120ub in replication fork dynamics. H2BK120ub is present at replication forks and accumulates upon replication stress in a manner dependent on ATR and RAD51. Loss of RNF20, the main ubiquitin ligase promoting H2BK120ub, leads to RECQ1-mediated unrestrained replication fork progression and defective fork reversal upon mild replication stress, restoring fork stability in BRCA2-deficient cells. Furthermore, we identified RNF169, a factor involved in the DNA damage response and repair, as a reader of the H2BK120ub mark at stalled replication forks, where it is required to protect the nascent DNA from excessive nucleolytic degradation. Hence, RNF20, H2BK120ub and RNF169 are key novel players orchestrating replication stress response and fork plasticity in human cells.

Indexed as

DNA ReplicationHistonesUbiquitin-Protein LigasesAtaxia Telangiectasia Mutated ProteinsDNA DamageHumansRad51 RecombinaseUbiquitinationAtaxia Telangiectasia Mutated ProteinsATR protein, humanHistonesRAD51 protein, humanRad51 RecombinaseRNF20 protein, humanUbiquitin-Protein LigasesDNA Replication Stress ResponseFork Plasticity and RestartHistone H2B UbiquitinationRNF169RNF20/RNF40

Identifiers

PMID41145912
PMCPMC12623888

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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.