Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model

Authors

  • Ali Entezam,

    1. Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
    2. Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, EX1 2LU Devon, United Kingdom
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  • Adihe Rachel Lokanga,

    1. Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
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  • Wei Le,

    1. Department of Biology, Morgan State University, Baltimore, Maryland
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  • Gloria Hoffman,

    1. Department of Biology, Morgan State University, Baltimore, Maryland
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  • Karen Usdin

    Corresponding author
    1. Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
    • National Institutes of Health, Building 8,k Room 202, 8 Center Drive, msc 0830, Bethesda, MD 20892-2189
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  • Communicated by Stylianos E. Antonarakis

Abstract

Tandem repeat expansion is responsible for the Repeat Expansion Diseases, a group of human genetic disorders that includes Fragile X syndrome (FXS). FXS results from expansion of a premutation (PM) allele having 55–200 CGG·CCG-repeats in the 5′ UTR of the FMR1 gene. The mechanism of expansion is unknown. We have treated FX PM mice with potassium bromate (KBrO3), a potent DNA oxidizing agent. We then monitored the germline and somatic expansion frequency in the progeny of these animals. We show here that KBrO3 increased both the level of 8-oxoG in the oocytes of treated animals and the germline expansion frequency. Our data thus suggest that oxidative damage may be a factor that could affect expansion risk in humans. Hum Mutat 31:1–6, 2010. Published 2010 Wiley-Liss, Inc.

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