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A novel Werner Syndrome mutation: pharmacological treatment by read-through of nonsense mutations and epigenetic therapies
- Publication Year :
- 2015
- Publisher :
- Taylor & Francis, 2015.
-
Abstract
- Werner Syndrome (WS) is a rare inherited disease characterized by premature aging and increased propensity for cancer. Mutations in the WRN gene can be of several types, including nonsense mutations, leading to a truncated protein form. WRN is a RecQ family member with both helicase and exonuclease activities, and it participates in several cell metabolic pathways, including DNA replication, DNA repair, and telomere maintenance. Here, we reported a novel homozygous WS mutation (c.3767 C > G) in 2 Argentinian brothers, which resulted in a stop codon and a truncated protein (p.S1256X). We also observed increased WRN promoter methylation in the cells of patients and decreased messenger WRN RNA (WRN mRNA) expression. Finally, we showed that the read-through of nonsense mutation pharmacologic treatment with both aminoglycosides (AGs) and ataluren (PTC-124) in these cells restores full-length protein expression and WRN functionality.
- Subjects :
- Premature aging
DNA Replication
Male
Cancer Research
congenital, hereditary, and neonatal diseases and abnormalities
DNA repair
Nonsense mutation
Apoptosis
Biology
medicine.disease_cause
Epigenesis, Genetic
chemistry.chemical_compound
medicine
Chromosomes, Human
Humans
Promoter Regions, Genetic
Molecular Biology
Cells, Cultured
Werner syndrome
Genetics
Protein Synthesis Inhibitors
Mutation
Oxadiazoles
nutritional and metabolic diseases
Aging, Premature
DNA Methylation
medicine.disease
Research Papers
Stop codon
Ataluren
Aminoglycosides
chemistry
Codon, Nonsense
DNA methylation
Cancer research
Female
Werner Syndrome
DNA Damage
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....714587ec39ab3bc2ca35923711efa26f