A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends

Mol Cell. 2007 May 11;26(3):323-34. doi: 10.1016/j.molcel.2007.03.023.

Abstract

The mechanisms by which telomeres are distinguished from DNA double-strand breaks are poorly understood. Here we have defined the minimal requirements for the protection of telomeric DNA ends from nonhomologous end-joining (NHEJ). Neither long, single-stranded overhangs nor t loop formation is essential to prevent NHEJ-mediated ligation of telomeric ends in vitro. Instead, a tandem array of 12 telomeric repeats is sufficient to impede illegitimate repair in a highly directional manner at nearby DNA ends. The polarity of end protection is consistent with the orientation of naturally occurring telomeres and is well suited to minimize interference between chromosome capping and the repair of DNA double-strand breaks in subtelomeric sequences. Biochemical fractionation and reconstitution revealed that telomere protection is mediated by a RAP1/TRF2 complex, providing evidence for a direct role for human RAP1 in the protection of telomeric DNA from NHEJ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chromosomal Instability / physiology
  • DNA Breaks, Double-Stranded*
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Directed Molecular Evolution / methods*
  • Evolution, Molecular
  • HeLa Cells
  • Humans
  • Models, Biological
  • Nuclear Proteins / physiology*
  • TATA Box Binding Protein-Like Proteins / physiology*
  • Telomere / metabolism*
  • Telomere-Binding Proteins / metabolism
  • Telomere-Binding Proteins / physiology*
  • Telomeric Repeat Binding Protein 2

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • TATA Box Binding Protein-Like Proteins
  • TERF2 protein, human
  • TERF2IP protein, human
  • Telomere-Binding Proteins
  • Telomeric Repeat Binding Protein 2