Evidence map›Paper›PMID 35768435›Full record

ArticleNature communications2022

WASp modulates RPA function on single-stranded DNA in response to replication stress and DNA damage.

Seong-Su Han, Kuo-Kuang Wen, María L García-Rubio, Marc S Wold, Andrés Aguilera, Wojciech Niedzwiedz, Yatin M Vyas

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
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

27 citing papers in PubMed, 35 citations in OpenAlex.

  1. The Role of Arp2/3 in End-Resection During DNA Double-Strand Break Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
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  5. Droplet Digital CRISPR for Nucleic Acid Detection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  7. Recent advances in nuclear actin research.Nucleus (Austin, Tex.) · 2025
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  12. Plasticity in leukocyte migration during haematopoiesis and inflammation.Journal of muscle research and cell motility · 2025
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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

7 authors at 4 institutions in 3 countries.

Seong-Su Han *Department of Pediatrics, PennState College of Medicine, PennState Health Children's Hospital, Hershey, PA, 17033, USA.
Kuo-Kuang Wen *Department of Pediatrics, PennState College of Medicine, PennState Health Children's Hospital, Hershey, PA, 17033, USA.
María L García-RubioAndalusian Center of Molecular Biology and Regenerative Medicine CABIMER, Department of Genome Biology, University of Seville-CSIC-University Pablo de Olavide, Seville, Spain.ORCID 0000-0003-0981-0555
Marc S WoldDepartment of Biochemistry and Molecular Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.ORCID 0000-0002-4580-1624
Andrés AguileraAndalusian Center of Molecular Biology and Regenerative Medicine CABIMER, Department of Genome Biology, University of Seville-CSIC-University Pablo de Olavide, Seville, Spain.ORCID 0000-0003-4782-1714
Wojciech NiedzwiedzThe Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK. wojciech.niedzwiedz@icr.ac.uk.ORCID 0000-0002-8518-6304
Yatin M VyasDepartment of Pediatrics, PennState College of Medicine, PennState Health Children's Hospital, Hershey, PA, 17033, USA. yvyas@pennstatehealth.psu.edu.ORCID 0000-0002-4595-0267
University of Iowa Stead Family Children’s Hospital · USCentro Andaluz de Biología Molecular y Medicina Regenerativa · ESInstitute of Cancer Research · GBUniversity of Iowa · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Jon C.D. Houtman · 2000 to 2026
$70.0M
Mechanisms of R loop-mediated genome instability in Wiskott-Aldrich syndromeR01AI146380 · NIAID · UNIVERSITY OF IOWA · PI VYAS, YATIN M · 2020 to 2024
$2.1M
Defining WASp-dependent pathways in replication stressR01AI177269 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI YATIN M VYAS · 2023 to 2026
$2.1M
Cancer Research UK A24881NIAID NIH HHS R01 AI146380NIAID NIH HHS R01 AI177269
6 · The paper itself

Abstract

Perturbation in the replication-stress response (RSR) and DNA-damage response (DDR) causes genomic instability. Genomic instability occurs in Wiskott-Aldrich syndrome (WAS), a primary immunodeficiency disorder, yet the mechanism remains largely uncharacterized. Replication protein A (RPA), a single-strand DNA (ssDNA) binding protein, has key roles in the RSR and DDR. Here we show that human WAS-protein (WASp) modulates RPA functions at perturbed replication forks (RFs). Following genotoxic insult, WASp accumulates at RFs, associates with RPA, and promotes RPA:ssDNA complexation. WASp deficiency in human lymphocytes destabilizes RPA:ssDNA-complexes, impairs accumulation of RPA, ATR, ETAA1, and TOPBP1 at genotoxin-perturbed RFs, decreases CHK1 activation, and provokes global RF dysfunction. las17 (yeast WAS-homolog)-deficient S. cerevisiae also show decreased ScRPA accumulation at perturbed RFs, impaired DNA recombination, and increased frequency of DNA double-strand break (DSB)-induced single-strand annealing (SSA). Consequently, WASp (or Las17)-deficient cells show increased frequency of DSBs upon genotoxic insult. Our study reveals an evolutionarily conserved, essential role of WASp in the DNA stress-resolution pathway, such that WASp deficiency provokes RPA dysfunction-coupled genomic instability.

Indexed as

DNA Breaks, Double-StrandedDNA ReplicationDNA, Single-StrandedReplication Protein ASaccharomyces cerevisiae ProteinsWiskott-Aldrich Syndrome ProteinAnimalsAntigens, SurfaceDNA-Binding ProteinsDNA RepairGenomic InstabilityHumansProtein BindingSaccharomyces cerevisiaeAntigens, SurfaceDNA-Binding ProteinsDNA, Single-StrandedETAA1 protein, humanLAS17 protein, S cerevisiaeReplication Protein ARPA1 protein, humanSaccharomyces cerevisiae ProteinsWAS protein, humanWiskott-Aldrich Syndrome Protein

Identifiers

PMID35768435
PMCPMC9243104
OpenAlexW4283696918

What OpenQuestion holds

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LicenceCC BY
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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.