ArticleAging2014
Serines 440 and 467 in the Werner syndrome protein are phosphorylated by DNA-PK and affects its dynamics in response to DNA double strand breaks.
Article in Aging, 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, 30 citations in OpenAlex.
- Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.Nature communications · 2025Article
- DNA-PK: A synopsis beyond synapsis.DNA repair · 2024Review
- Monitoring nucleolar-nucleoplasmic protein shuttling in living cells by high-content microscopy and automated image analysis.Nucleic acids research · 2024Article
- 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
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- RecQ Helicase Somatic Alterations in Cancer.Frontiers in molecular biosciences · 2022Review
- Human RecQ Helicases in DNA Double-Strand Break Repair.Frontiers in cell and developmental biology · 2021Review
- RecQ helicases in DNA repair and cancer targets.Essays in biochemistry · 2020Review
- Review
- The Nucleolus and PARP1 in Cancer Biology.Cancers · 2020Review
- PARP1 regulates DNA damage-induced nucleolar-nucleoplasmic shuttling of WRN and XRCC1 in a toxicant and protein-specific manner.Scientific reports · 2019Article
- Acetylation of Werner protein at K1127 and K1117 is important for nuclear trafficking and DNA repair.DNA repair · 2019Article
- Werner Syndrome Protein and DNA Replication.International journal of molecular sciences · 2018Review
- Recent Advances in Understanding Werner Syndrome.F1000Research · 2017Review
- Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions.Ageing research reviews · 2017Review
- Different non-synonymous polymorphisms modulate the interaction of the WRN protein to its protein partners and its enzymatic activities.Oncotarget · 2016Article
- CDK1 phosphorylates WRN at collapsed replication forks.Nature communications · 2016Article
- Replication stress induced site-specific phosphorylation targets WRN to the ubiquitin-proteasome pathway.Oncotarget · 2016Article
- DNA-PK: a dynamic enzyme in a versatile DSB repair pathway.DNA repair · 2014Review
- Catalytic activities of Werner protein are affected by adduction with 4-hydroxy-2-nonenal.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
WRN protein, defective in Werner syndrome (WS), a human segmental progeria, is a target of serine/threonine kinases involved in sensing DNA damage. DNA-PK phosphorylates WRN in response to DNA double strand breaks (DSBs). However, the main phosphorylation sites and functional importance of the phosphorylation of WRN has remained unclear. Here, we identify Ser-440 and -467 in WRN as major phosphorylation sites mediated by DNA-PK.In vitro, DNA-PK fails to phosphorylate a GST-WRN fragment with S440A and/or S467A substitution. In addition, full length WRN with the mutation expressed in 293T cells was not phosphorylated in response to DSBs produced by bleomycin. Accumulation of the mutant WRN at the site of laser-induced DSBs occurred with the same kinetics as wild type WRN in live HeLa cells. While the wild type WRN relocalized to the nucleoli after 24 hours recovery from etoposide-induced DSBs, the mutant WRN remained mostly in the nucleoplasm. Consistent with this, WS cells expressing the mutants exhibited less DNA repair efficiency and more sensitivity to etoposide, compared to those expressing wild type. Our findings indicate that phosphorylation of Ser-440 and -467 in WRN are important for relocalization of WRN to nucleoli, and that it is required for efficient DSB repair.
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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.