ArticleNucleic acids research2015
The WRN exonuclease domain protects nascent strands from pathological MRE11/EXO1-dependent degradation.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 85 citations in OpenAlex.
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.Nature communications · 2026Article
- Structural basis of Ku-mediated activation of WRN exonuclease activity.Nature communications · 2026Article
- A mutational scar-based genome-wide map of DNA double-strand break repair.Nature communications · 2026Article
- The BRCA1-A complex restricts replication fork reversal-dependent DNA repair in ATM deficient cells.bioRxiv : the preprint server for biology · 2026Article
- The function of Mgs1/WRNIP1 in genome maintenance.Frontiers in molecular biosciences · 2026Review
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Review
- PLK1 phosphorylates WRN at replication forks.The Journal of pharmacology and experimental therapeutics · 2025Article
- Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.Nature communications · 2025Article
- Switch-like phosphorylation of WRN integrates end-resection with RAD51 metabolism at collapsed replication forks.Nucleic acids research · 2024Article
- USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.Nature communications · 2024Article
- RAD52 prevents accumulation ofbioRxiv : the preprint server for biology · 2024Article
- Response to Replication Stress and Maintenance of Genome Stability by WRN, the Werner Syndrome Protein.International journal of molecular sciences · 2024Review
- Replication stress as a driver of cellular senescence and aging.Communications biology · 2024Review
- CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection.Nature communications · 2023Article
- PHOSPHORYLATION-DEPENDENT ASSOCIATION OF WRN WITH RPA IS REQUIRED FOR RECOVERY OF REPLICATION FORKS STALLED AT SECONDARY DNA STRUCTURES.bioRxiv : the preprint server for biology · 2023Article
- Phosphorylation status of MUS81 is a modifier of Olaparib sensitivity in BRCA2-deficient cells.Nucleic acids research · 2023Article
- Article
- Replication fork uncoupling causes nascent strand degradation and fork reversal.Nature structural & molecular biology · 2023Article
- WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The WRN helicase/exonuclease protein is required for proper replication fork recovery and maintenance of genome stability. However, whether the different catalytic activities of WRN cooperate to recover replication forks in vivo is unknown. Here, we show that, in response to replication perturbation induced by low doses of the TOP1 inhibitor camptothecin, loss of the WRN exonuclease resulted in enhanced degradation and ssDNA formation at nascent strands by the combined action of MRE11 and EXO1, as opposed to the limited processing of nascent strands performed by DNA2 in wild-type cells. Nascent strand degradation by MRE11/EXO1 took place downstream of RAD51 and affected the ability to resume replication, which correlated with slow replication rates in WRN exonuclease-deficient cells. In contrast, loss of the WRN helicase reduced exonucleolytic processing at nascent strands and led to severe genome instability. Our findings identify a novel role of the WRN exonuclease at perturbed forks, thus providing the first in vivo evidence for a distinct action of the two WRN enzymatic activities upon fork stalling and providing insights into the pathological mechanisms underlying the processing of perturbed forks.
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Registered trials
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.