Research Article

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

  1. Ali Entezam1,2,
  2. Adihe Rachel Lokanga1,
  3. Wei Le3,
  4. Gloria Hoffman3,
  5. Karen Usdin1,*

Article first published online: 8 MAR 2010

DOI: 10.1002/humu.21237

Issue

Human Mutation

Human Mutation

Volume 31, Issue 5, pages 611–616, May 2010

Additional Information

How to Cite

Entezam, A., Lokanga, A. R., Le, W., Hoffman, G. and Usdin, K. (2010), Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model. Hum. Mutat., 31: 611–616. doi: 10.1002/humu.21237

Author Information

  1. 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. 2

    Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, EX1 2LU Devon, United Kingdom

  3. 3

    Department of Biology, Morgan State University, Baltimore, Maryland

*National Institutes of Health, Building 8,k Room 202, 8 Center Drive, msc 0830, Bethesda, MD 20892-2189

  1. †

    Communicated by Stylianos E. Antonarakis

Publication History

  1. Issue published online: 29 APR 2010
  2. Article first published online: 8 MAR 2010
  3. Accepted manuscript online: 8 MAR 2010 12:00AM EST
  4. Manuscript Revised: 2 MAR 2010
  5. Manuscript Received: 4 SEP 2009

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Keywords:

  • repeat expansion disease;
  • triplet repeat instability;
  • Fragile X syndrome;
  • FMR1;
  • DNA repair;
  • oxidative damage;
  • 7;
  • 8-dihydro-8-oxo-guanine (8-oxoG)

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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