A higher-order entity formed by the flexible assembly of RAP1 with TRF2

Nucleic Acids Res. 2016 Feb 29;44(4):1962-76. doi: 10.1093/nar/gkv1531. Epub 2016 Jan 8.


Telomere integrity is essential to maintain genome stability, and telomeric dysfunctions are associated with cancer and aging pathologies. In human, the shelterin complex binds TTAGGG DNA repeats and provides capping to chromosome ends. Within shelterin, RAP1 is recruited through its interaction with TRF2, and TRF2 is required for telomere protection through a network of nucleic acid and protein interactions. RAP1 is one of the most conserved shelterin proteins although one unresolved question is how its interaction may influence TRF2 properties and regulate its capacity to bind multiple proteins. Through a combination of biochemical, biophysical and structural approaches, we unveiled a unique mode of assembly between RAP1 and TRF2. The complete interaction scheme between the full-length proteins involves a complex biphasic interaction of RAP1 that directly affects the binding properties of the assembly. These results reveal how a non-DNA binding protein can influence the properties of a DNA-binding partner by mutual conformational adjustments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Damage / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Genomic Instability*
  • Humans
  • Multiprotein Complexes
  • Protein Binding
  • Shelterin Complex
  • Telomere / genetics
  • Telomere-Binding Proteins / chemistry
  • Telomere-Binding Proteins / genetics*
  • Telomere-Binding Proteins / metabolism
  • Telomeric Repeat Binding Protein 2 / chemistry
  • Telomeric Repeat Binding Protein 2 / genetics*
  • Telomeric Repeat Binding Protein 2 / metabolism


  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Shelterin Complex
  • TERF2 protein, human
  • TERF2IP protein, human
  • Telomere-Binding Proteins
  • Telomeric Repeat Binding Protein 2