title: Long CGG-repeat tracts are toxic to human cells: implications for carriers of Fragile X premutation alleles.
abstract: People with 59-200 CGG.CCG-repeats in the 5' UTR of one of their FMR1 genes are at risk for Fragile X tremor and ataxia syndrome. Females are also at risk for premature ovarian failure. These symptoms are thought to be due to the presence of the repeats at the DNA and/or RNA level. We show here that long transcribed but untranslated CGG-repeat tracts are toxic to human cells and alter the expression of a wide variety of different genes including caspase-8, CYFIP, Neurotensin and UBE3A.
authors.affiliation: Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Handa
authors.forename: Deena
authors.initials: D
authors.lastname: Goldwater
authors.forename: David
authors.initials: D
authors.lastname: Stiles
authors.forename: Margaret
authors.initials: M
authors.lastname: Cam
authors.forename: George
authors.initials: G
authors.lastname: Poy
authors.forename: Daman
authors.initials: D
authors.lastname: Kumari
authors.forename: Karen
authors.initials: K
authors.lastname: Usdin
mesh_terms: D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D017304:Annexin A5 / Q000187:drug effects / Q000378:metabolism; D001259:Ataxia / Q000235:genetics; D015153:Blotting, Western; D053181:Caspase 8; D020169:Caspases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006540:Herbicides / Q000494:pharmacology; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010269:Paraquat / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D019680:Trinucleotide Repeat Expansion / Q000187:drug effects* / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D017304:Annexin A5; C109916:CYFIP1 protein, human; D016895:Culture Media, Serum-Free; D006540:Herbicides; D009496:Neurotensin; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases; D019311:Staurosporine; D004318:Doxycycline; D010269:Paraquat