Evidence map›Paper›PMID 36593312›Full record

ArticleNature structural & molecular biology2023

Replication fork uncoupling causes nascent strand degradation and fork reversal.

Tamar Kavlashvili, Wenpeng Liu, Taha M Mohamed, David Cortez, James M Dewar

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing 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

20 citing papers in PubMed.

  1. Article
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  5. Reconstitution of genome remodeling usingFrontiers in cell and developmental biology · 2026
    Review
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  8. Article
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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

5 authors.

Tamar KavlashviliDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
Wenpeng LiuDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
Taha M MohamedDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
David CortezDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-0154-140X
James M DewarDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA. james.dewar@vanderbilt.edu.ORCID http://orcid.org/0000-0003-4153-3818

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Mechanisms that ensure the completion of DNA synthesisR35GM128696 · NIGMS · VANDERBILT UNIVERSITY · PI James M Dewar · 2018 to 2026
$4.0M
NCI NIH HHS P30 CA068485NIGMS NIH HHS R35 GM128696
6 · The paper itself

Abstract

Genotoxins cause nascent strand degradation (NSD) and fork reversal during DNA replication. NSD and fork reversal are crucial for genome stability and are exploited by chemotherapeutic approaches. However, it is unclear how NSD and fork reversal are triggered. Additionally, the fate of the replicative helicase during these processes is unknown. We developed a biochemical approach to study synchronous, localized NSD and fork reversal using Xenopus egg extracts and validated this approach with experiments in human cells. We show that replication fork uncoupling stimulates NSD of both nascent strands and progressive conversion of uncoupled forks to reversed forks. Notably, the replicative helicase remains bound during NSD and fork reversal. Unexpectedly, NSD occurs before and after fork reversal, indicating that multiple degradation steps take place. Overall, our data show that uncoupling causes NSD and fork reversal and elucidate key events that precede fork reversal.

Indexed as

DNA-Binding ProteinsDNA ReplicationAnimalsDNA HelicasesGenomic InstabilityHumansXenopus laevisDNA-Binding ProteinsDNA Helicases

Identifiers

PMID36593312
PMCPMC9868089

What OpenQuestion holds

Textmetadata
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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.