Evidence map›Paper›PMID 41646390›Full record

ArticleResearch square2026

Fork Reversal Safeguards Epigenetic Inheritance During Replication Stress.

Qiong Wu, Caixian Zhou, Yue Dou, Nadia I Martin, Maria Gwit, Tae-Hee Lee, Mark Hedglin, Roséa Chen, Ke Zhu, Tianpeng Zhang and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2026. 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

14 authors.

Qiong WuDepartment of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Caixian ZhouDepartment of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.ORCID 0009-0000-4641-7301
Yue DouDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Nadia I MartinDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Maria GwitDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Tae-Hee LeeDepartment of Chemistry, The Pennsylvania State University, University Park, PA 16802.ORCID 0000-0003-2034-6394
Mark HedglinDepartment of Chemistry, The Pennsylvania State University, University Park, PA 16802.ORCID 0000-0003-2599-1691
Roséa ChenDepartment of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Ke ZhuDepartment of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Tianpeng ZhangDepartment of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Shangming TangDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Tian ZhangDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.ORCID 0000-0001-9007-7965
Tyler M WeaverDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Wenpeng LiuDepartment of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.ORCID 0000-0002-2139-4104

Funding

Deciphering the progression and regulation of human translesion DNA synthesisR35GM147238 · NIGMS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI Mark Hedglin · 2022 to 2026
$2.0M
NIGMS NIH HHS R35 GM147238
6 · The paper itself

Abstract

During DNA replication, epigenetic information carried by histone modifications is faithfully propagated and re-established on sister chromatids, ensuring cell identity. Chromatin reassembly is tightly coupled to DNA replication, however, whether and how perturbations to DNA replication affects the fidelity of epigenetic inheritance remain unclear. In this study, we reveal a critical role for replication fork reversal in maintaining the transmission of epigenetic information under replication stress. Cells defective in fork reversal exhibit reduced nucleosome density at replication forks, accompanied by the loss of parental histones during their transfer onto nascent DNA. Mechanistically, we demonstrate that PrimPol activation leads to single-stranded DNA gaps in fork reversal deficient cells, and that subsequent PARylation (poly ADP-ribosylation) and DNA-protein crosslinking on these gaps cause nucleosomes loss. Our findings demonstrate that replication fork reversal, a widespread physiological process, is not only essential for preserving genome integrity but also for safeguarding epigenetic stability.

Identifiers

PMID41646390
PMCPMC12869582

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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.