Evidence map›Paper›PMID 36711944›Full record

ArticlebioRxiv : the preprint server for biology2023

Actin nucleators safeguard replication forks by limiting nascent strand degradation.

Jadwiga Nieminuszczy, Peter R Martin, Ronan Broderick, Joanna Krwawicz, Alexandra Kanellou, Camelia Mocanu, Vicky Bousgouni, Charlotte Smith, Kuo-Kuang Wen, Beth L Woodward and 6 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 3 countries.

Jadwiga NieminuszczyCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Peter R MartinCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Ronan BroderickCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Joanna KrwawiczCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Alexandra KanellouCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Camelia MocanuCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Vicky BousgouniCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Charlotte SmithCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Kuo-Kuang WenDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, PennState College of Medicine, PennState Health Children's Hospital, Hershey, Pennsylvania 17033, USA.
Beth L WoodwardGenome Stability and Human Disease Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Chris BakalCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Fiona ShackleyPaediatric Immunology, Allergy and Infectious Diseases, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK.
Andres AguileraCentro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Seville, Spain.
Grant S StewartGenome Stability and Human Disease Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Yatin M VyasDepartment of Pediatrics, Division of Pediatric Hematology-Oncology, PennState College of Medicine, PennState Health Children's Hospital, Hershey, Pennsylvania 17033, USA.
Wojciech NiedzwiedzCancer Biology, The Institute of Cancer Research, London, SW3 6JB, UK.
Institute of Cancer Research · GBPenn State Milton S. Hershey Medical Center · USUniversity of Birmingham · GBCentro Andaluz de Biología Molecular y Medicina Regenerativa · ESSheffield Children's Hospital · GB

Funding

Mechanisms of R loop-mediated genome instability in Wiskott-Aldrich syndromeR01AI146380 · NIAID · UNIVERSITY OF IOWA · PI VYAS, YATIN M · 2020 to 2024
$2.1M
Cancer Research UK 24881NIAID NIH HHS R01 AI146380
6 · The paper itself

Abstract

Accurate genome replication is essential for all life and a key mechanism of disease prevention, underpinned by the ability of cells to respond to replicative stress (RS) and protect replication forks. These responses rely on the formation of Replication Protein A (RPA)-single stranded (ss) DNA complexes, yet this process remains largely uncharacterized. Here we establish that actin nucleation-promoting factors (NPFs) associate with replication forks, promote efficient DNA replication and facilitate association of RPA with ssDNA at sites of RS. Accordingly, their loss leads to deprotection of ssDNA at perturbed forks, impaired ATR activation, global replication defects and fork collapse. Supplying an excess of RPA restores RPA foci formation and fork protection, suggesting a chaperoning role for actin nucleators (ANs) (i.e., Arp2/3, DIAPH1) and NPFs (i.e, WASp, N-WASp) in regulating RPA availability upon RS. We also discover that β-actin interacts with RPA directly

Identifiers

PMID36711944
PMCPMC9882250
OpenAlexW4316041285

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.