Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model.
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 (KBrO(3)), a potent DNA oxidizing agent. We then monitored the germline and somatic expansion frequency in the progeny of these animals. We show here that KBrO(3) 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.
Entezam
Ali
A
Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda, MD 20892, USA.
Lokanga
Adihe Rachel
AR
Le
Wei
W
Hoffman
Gloria
G
Usdin
Karen
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001959:Bromates / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D045585:Flap Endonucleases / Q000235:genetics; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020080:Tandem Repeat Sequences; D019680:Trinucleotide Repeat Expansion / Q000187:drug effects / Q000235:genetics*
D001959:Bromates; C019536:potassium bromate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045585:Flap Endonucleases; D003849:Deoxyguanosine