Back to the future: The intimate and evolving connection between telomere-related factors and genotoxic stress

J Biol Chem. 2019 Oct 4;294(40):14803-14813. doi: 10.1074/jbc.AW119.008145. Epub 2019 Aug 21.


The conversion of circular genomes to linear chromosomes during molecular evolution required the invention of telomeres. This entailed the acquisition of factors necessary to fulfill two new requirements: the need to fully replicate terminal DNA sequences and the ability to distinguish chromosome ends from damaged DNA. Here we consider the multifaceted functions of factors recruited to perpetuate and stabilize telomeres. We discuss recent theories for how telomere factors evolved from existing cellular machineries and examine their engagement in nontelomeric functions such as DNA repair, replication, and transcriptional regulation. We highlight the remarkable versatility of protection of telomeres 1 (POT1) proteins that was fueled by gene duplication and divergence events that occurred independently across several eukaryotic lineages. Finally, we consider the relationship between oxidative stress and telomeres and the enigmatic role of telomere-associated proteins in mitochondria. These findings point to an evolving and intimate connection between telomeres and cellular physiology and the strong drive to maintain chromosome integrity.

Keywords: CST; DNA replication; POT1; chromosome ends; genome integrity; molecular evolution; oxidative damage; protection Of telomeres 1; shelterin; telomerase; telomerase reverse transcriptase (TERT); telomere repeat.

Publication types

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

MeSH terms

  • DNA Damage / genetics*
  • DNA Repair / genetics
  • Eukaryotic Cells
  • Gene Expression Regulation / genetics
  • Humans
  • Mitochondria / genetics
  • Oxidative Stress / genetics
  • Telomerase / genetics
  • Telomere / genetics*
  • Telomere-Binding Proteins / genetics*


  • POT1 protein, human
  • Telomere-Binding Proteins
  • Telomerase