Evidence map›Paper›PMID 40764480›Full record

ArticleNature communications2025

The RING finger E3 ligase RNF25 protects DNA replication forks independently of its canonical roles in ubiquitin signaling.

Lilly F Chiou, Gaith N Droby, Deepika Jayaprakash, Jay R Anand, Xingyuan Zhang, Yang Yang, C Allie Mills, Thomas S Webb, Natalie K Barker, Jialiu Xie and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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

5 · Who and what money

Authors and funding

15 authors.

Lilly F ChiouCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-9437-1475
Gaith N DrobyCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-0116-0340
Deepika JayaprakashDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jay R AnandDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-2071-9891
Xingyuan ZhangDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Yang YangDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-5936-4090
C Allie MillsUNC Metabolomics & Proteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Thomas S WebbUNC Metabolomics & Proteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Natalie K BarkerUNC Metabolomics & Proteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jialiu XieDepartment of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-0560-7982
Di WuDivision of Oral and Craniofacial Health Science, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-8331-2357
Laura E HerringUNC Metabolomics & Proteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-4496-7312
Junya TomidaDepartment of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA.ORCID http://orcid.org/0000-0002-0813-5757
Jessica L BowserDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cyrus VaziriDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. cyrus_vaziri@med.unc.edu.ORCID http://orcid.org/0000-0002-3081-8685

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
NRSA in GeneticsT32GM135128 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Daniel J McKay, JEFF J. SEKELSKY · 2020 to 2026
$5.1M
Defining Mechanisms of Pathological Trans-Lesion Synthesis During CarcinogenesisR01CA215347 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VAZIRI, CYRUS, WILLIAMS, SCOTT E · 2018 to 2022
$2.6M
Pathological Reprogramming of DNA Damage Signaling in Neoplastic CellsR01ES029079 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEARCE, KENNETH HUGH, VAZIRI, CYRUS · 2019 to 2023
$2.3M
Andor Dragonfly 202 Spinning Disk Confocal Microscope for the University of North Carolina at Chapel HillS10OD030223 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ARIEL, PABLO · 2021 to 2021
$474k
NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA215347NIEHS NIH HHS R01 ES029079NIGMS NIH HHS T32 GM135128NIH HHS S10 OD030223U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 5T32GM135128
6 · The paper itself

Abstract

The DNA damage response (DDR) mechanisms that allow cells to tolerate DNA replication stress are critically important for genome stability and cell viability. Using an unbiased genetic screen, we identify a role for the RING finger E3 ubiquitin ligase RNF25 in promoting DNA replication stress tolerance. In response to DNA replication stress, RNF25-deficient cells generate aberrantly high levels of single-stranded DNA (ssDNA), accumulate in S-phase and show reduced mitotic entry. Using single-molecule DNA fiber analysis, we show that RNF25 protects reversed DNA replication forks generated by the fork remodeler HLTF from nucleolytic degradation by MRE11 and CtIP. Mechanistically, RNF25 interacts with the replication fork protection factor REV7 and recruits REV7 to nascent DNA after replication stress. The role of RNF25 in protecting replication forks is fully separable from its canonical functions in ubiquitin conjugation. This work reveals the RNF25-REV7 signaling axis as an important protective mechanism in cells experiencing replication stress.

Indexed as

DNA ReplicationUbiquitinUbiquitin-Protein LigasesCarrier ProteinsDNA-Binding ProteinsDNA DamageDNA, Single-StrandedHeLa CellsHumansMRE11 Homologue ProteinNuclear ProteinsSignal TransductionTranscription FactorsCarrier ProteinsDNA-Binding ProteinsDNA, Single-StrandedHLTF protein, humanMRE11 Homologue ProteinMRE11 protein, humanNuclear ProteinsTranscription FactorsUbiquitinUbiquitin-Protein Ligases

Identifiers

PMID40764480
PMCPMC12325937

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.