A TRF1-controlled common fragile site containing interstitial telomeric sequences

Chromosoma. 2012 Oct;121(5):465-74. doi: 10.1007/s00412-012-0377-6. Epub 2012 Jul 13.

Abstract

Mouse telomeres have been suggested to resemble common fragile sites (CFS), showing disrupted TTAGGG fluorescent in situ hybridization signals after aphidicolin treatment. This "fragile" telomere phenotype is induced by deletion of TRF1, a shelterin protein that binds telomeric DNA and promotes efficient replication of the telomeric ds[TTAGGG]n tracts. Here we show that the chromosome-internal TTAGGG repeats present at human chromosome 2q14 form an aphidicolin-induced CFS. TRF1 binds to and stabilizes CFS 2q14 but does not affect other CFS, establishing 2q14 as the first CFS controlled by a sequence-specific DNA binding protein. The data show that telomeric DNA is inherently fragile regardless of its genomic position and imply that CFS can be caused by a specific DNA sequence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Chromosomal Instability
  • Chromosome Fragile Sites*
  • Chromosomes, Human, Pair 2 / genetics
  • Chromosomes, Human, Pair 2 / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomeric Repeat Binding Protein 1 / genetics
  • Telomeric Repeat Binding Protein 1 / metabolism*

Substances

  • Telomeric Repeat Binding Protein 1