ArticleHuman molecular genetics2016
The Werner syndrome RECQ helicase targets G4 DNA in human cells to modulate transcription.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 99 citations in OpenAlex.
- Development of an exon 27-skipping antisense oligonucleotide as a targeted therapy for refractory skin ulcers in Werner syndrome.Molecular therapy. Nucleic acids · 2026Article
- Strand-asymmetric G-runs and G4s downstream of TSS modulate tumor suppressor gene transcription.Oncogene · 2026Article
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- BMI1 represses G-quadruplex DNA formation to maintain genomic stability during replication.The Journal of biological chemistry · 2026Article
- ssG4-seq for global profiling of strand-specific G-quadruplex structures in mammalian genomes.Nature communications · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Review
- Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines.ACS bio & med chem Au · 2025Article
- Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.Nature communications · 2025Article
- Amelioration of premature aging in Werner syndrome stem cells by targeting SHIP/AKT pathway.Cell & bioscience · 2025Article
- Article
- Review
- Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles.International journal of molecular sciences · 2024Review
- Guardians of the Genome: How the Single-Stranded DNA-Binding Proteins RPA and CST Facilitate Telomere Replication.Biomolecules · 2024Review
- Alternative DNA structures in hematopoiesis and adaptive immunity.Advances in immunology · 2024Review
- 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
- hSSB1 (NABP2/OBFC2B) modulates the DNA damage and androgen-induced transcriptional response in prostate cancer.The Prostate · 2023Article
- DNA/RNA helicase DHX36 is required for late stages of spermatogenesis.Journal of molecular cell biology · 2023Article
- Discovery of a new hereditary RECQ helicase disorder RECON syndrome positions the replication stress response and genome homeostasis as centrally important processes in aging and age-related disease.Ageing research reviews · 2023Review
- G-quadruplexes and associated proteins in aging and Alzheimer's disease.Frontiers in aging · 2023Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The Werner syndrome (WS) is a prototypic adult Mendelian progeroid syndrome in which signs of premature aging are associated with genomic instability and an elevated risk of cancer. The WRN RECQ helicase protein binds and unwinds G-quadruplex (G4) DNA substrates in vitro, and we identified significant enrichment in G4 sequence motifs at the transcription start site and 5' ends of first introns (false discovery rate < 0.001) of genes down-regulated in WS patient fibroblasts. This finding provides strong evidence that WRN binds G4 DNA structures at many chromosomal sites to modulate gene expression. WRN appears to bind a distinct subpopulation of G4 motifs in human cells, when compared with the related Bloom syndrome RECQ helicase protein. Functional annotation of the genes and miRNAs altered in WS provided new insight into WS disease pathogenesis. WS patient fibroblasts displayed altered expression of multiple, mechanistically distinct, senescence-associated gene expression programs, with altered expression of disease-associated miRNAs, and dysregulation of canonical pathways that regulate cell signaling, genome stability and tumorigenesis. WS fibroblasts also displayed a highly statistically significant and distinct gene expression signature, with coordinate overexpression of nearly all of the cytoplasmic tRNA synthetases and associated ARS-interacting multifunctional protein genes. The 'non-canonical' functions of many of these upregulated tRNA charging proteins may together promote WS disease pathogenesis. Our results identify the human WRN RECQ protein as a G4 helicase that modulates gene expression in G4-dependent fashion at many chromosomal sites and provide several new and unexpected mechanistic insights into WS disease pathogenesis.
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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.