An origin of DNA replication in the promoter region of the human fragile X mental retardation (FMR1) gene Academic Article uri icon


MeSH Major

  • DNA Replication
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome
  • Promoter Regions, Genetic
  • Replication Origin


  • Fragile X syndrome, the most common form of inherited mental retardation in males, arises when the normally stable 5 to 50 CGG repeats in the 5' untranslated region of the fragile X mental retardation protein 1 (FMR1) gene expand to over 200, leading to DNA methylation and silencing of the FMR1 promoter. Although the events that trigger local CGG expansion remain unknown, the stability of trinucleotide repeat tracts is affected by their position relative to an origin of DNA replication in model systems. Origins of DNA replication in the FMR1 locus have not yet been described. Here, we report an origin of replication adjacent to the FMR1 promoter and CGG repeats that was identified by scanning a 35-kb region. Prereplication proteins Orc3p and Mcm4p bind to chromatin in the FMR1 initiation region in vivo. The position of the FMR1 origin relative to the CGG repeats is consistent with a role in repeat maintenance. The FMR1 origin is active in transformed cell lines, fibroblasts from healthy individuals, fibroblasts from patients with fragile X syndrome, and fetal cells as early as 8 weeks old. The potential role of the FMR1 origin in CGG tract instability is discussed.

publication date

  • January 2007



  • Academic Article



  • eng

PubMed Central ID

  • PMC1800797

Digital Object Identifier (DOI)

  • 10.1128/MCB.01382-06

PubMed ID

  • 17101793

Additional Document Info

start page

  • 426

end page

  • 37


  • 27


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