ArticleNucleic acids research2014
Checkpoint-dependent and independent roles of the Werner syndrome protein in preserving genome integrity in response to mild replication stress.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype.Scientific reports · 2017Trial
- Identification of a Proteolysis-Targeting-Chimera that Addresses Activated Checkpoint Kinase-1 Reveals its Non-Catalytic Functions in Tumor Cells.Angewandte Chemie (International ed. in English) · 2025Article
- Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.Nature communications · 2025Article
- Article
- 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
- Noncanonical Roles of RAD51.Cells · 2023Review
- Synthetical lethality of Werner helicase and mismatch repair deficiency is mediated by p53 and PUMA in colon cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1.International journal of molecular sciences · 2022Review
- Checkpoint functions of RecQ helicases at perturbed DNA replication fork.Current genetics · 2021Review
- Article
- History of DNA Helicases.Genes · 2020Review
- Checkpoint Defects Elicit a WRNIP1-Mediated Response to Counteract R-Loop-Associated Genomic Instability.Cancers · 2020Article
- ATM pathway activation limits R-loop-associated genomic instability in Werner syndrome cells.Nucleic acids research · 2019Article
- Article
- RecQ and Fe-S helicases have unique roles in DNA metabolism dictated by their unwinding directionality, substrate specificity, and protein interactions.Biochemical Society transactions · 2018Review
- The essential kinase ATR: ensuring faithful duplication of a challenging genome.Nature reviews. Molecular cell biology · 2017Review
- Review
- CDK1 phosphorylates WRN at collapsed replication forks.Nature communications · 2016Article
- WRNIP1 protects stalled forks from degradation and promotes fork restart after replication stress.The EMBO journal · 2016Article
- Replication stress induced site-specific phosphorylation targets WRN to the ubiquitin-proteasome pathway.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Werner syndrome (WS) is a human chromosomal instability disorder associated with cancer predisposition and caused by mutations in the WRN gene. WRN helicase activity is crucial in limiting breakage at common fragile sites (CFS), which are the preferential targets of genome instability in precancerous lesions. However, the precise function of WRN in response to mild replication stress, like that commonly used to induce breaks at CFS, is still missing. Here, we establish that WRN plays a role in mediating CHK1 activation under moderate replication stress. We provide evidence that phosphorylation of CHK1 relies on the ATR-mediated phosphorylation of WRN, but not on WRN helicase activity. Analysis of replication fork dynamics shows that loss of WRN checkpoint mediator function as well as of WRN helicase activity hamper replication fork progression, and lead to new origin activation to allow recovery from replication slowing upon replication stress. Furthermore, bypass of WRN checkpoint mediator function through overexpression of a phospho-mimic form of CHK1 restores fork progression and chromosome stability to the wild-type levels. Together, these findings are the first demonstration that WRN regulates the ATR-checkpoint activation upon mild replication stress, preventing chromosome fragility.
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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.