The Response to DNA Damage at Telomeric Repeats and Its Consequences for Telomere Function

Genes (Basel). 2019 Apr 24;10(4):318. doi: 10.3390/genes10040318.

Abstract

Telomeric repeats, coated by the shelterin complex, prevent inappropriate activation of the DNA damage response at the ends of linear chromosomes. Shelterin has evolved distinct solutions to protect telomeres from different aspects of the DNA damage response. These solutions include formation of t-loops, which can sequester the chromosome terminus from DNA-end sensors and inhibition of key steps in the DNA damage response. While blocking the DNA damage response at chromosome ends, telomeres make wide use of many of its players to deal with exogenous damage and replication stress. This review focuses on the interplay between the end-protection functions and the response to DNA damage occurring inside the telomeric repeats, as well as on the consequences that telomere damage has on telomere structure and function.

Keywords: alternative lengthening of telomeres; end-protection problem; shelterin complex; telomere damage; telomere maintenance; telomere replication; telomeric double strand breaks.

Publication types

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

MeSH terms

  • Animals
  • DNA Damage
  • DNA Repair*
  • Humans
  • Telomere / genetics*
  • Telomere / metabolism*
  • Telomere Homeostasis
  • Telomere-Binding Proteins / metabolism

Substances

  • Telomere-Binding Proteins