No DDRama at chromosome ends: TRF2 takes centre stage

Trends Biochem Sci. 2015 May;40(5):275-85. doi: 10.1016/j.tibs.2015.03.003. Epub 2015 Apr 3.


Telomeres are nucleoprotein structures capping the natural termini of eukaryotic linear chromosomes. Telomeres possess an inherent ability to circumvent the activation of a full-blown DNA damage response (DDR), and hence fusion reactions, by limiting inappropriate double-strand break (DSB) repair and processing activities at eukaryotic chromosome ends. A telomere-specific protein complex, termed shelterin, has a crucial function in safeguarding and securing telomere integrity. Within this complex, TRF2 has emerged as the key player, dictating different states of telomere protection during the replicative lifespan of a cell. How TRF2 prevents activation of DSB repair activities at functional telomeres has now been extensively investigated. In this review we aim at exploring the complex and multi-faceted mechanisms underlying the TRF2-mediated protection of eukaryotic chromosome ends.

Keywords: DNA damage response; TERRA; TRF2; chromatin; t-loops; telomeres.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Chromosomes / metabolism*
  • DNA Damage / genetics
  • DNA Damage / physiology
  • DNA Repair / genetics
  • DNA Repair / physiology
  • Humans
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism*


  • Chromatin
  • Telomeric Repeat Binding Protein 2