Telomeres in toxicology: Occupational health

Pharmacol Ther. 2021 Apr;220:107742. doi: 10.1016/j.pharmthera.2020.107742. Epub 2020 Nov 8.

Abstract

The ends of chromosomes shorten at each round of cell division, and this process is thought to be affected by occupational exposures. Occupational hazards may alter telomere length homeostasis resulting in DNA damage, chromosome aberration, mutations, epigenetic alterations and inflammation. Therefore, for the protection of genetic material, nature has provided a unique nucleoprotein structure known as a telomere. Telomeres provide protection by averting an inappropriate activation of the DNA damage response (DDR) at chromosomal ends and preventing recognition of single and double strand DNA (ssDNA and dsDNA) breaks or chromosomal end-to-end fusion. Telomeres and their interacting six shelterin complex proteins in coordination act as inhibitors of DNA damage machinery by blocking DDR activation at chromosomes, thereby preventing the occurrence of genome instability, perturbed cell cycle, cellular senescence and apoptosis. However, inappropriate DNA repair may result in the inadequate distribution of genetic material during cell division, resulting in the eventual development of tumorigenesis and other pathologies. This article reviews the current literature on the association of changes in telomere length and its interacting proteins with different occupational exposures and the potential application of telomere length or changes in the regulatory proteins as potential biomarkers for exposure and health response, including recent findings and future perspectives.

Keywords: DNA damage; DNA damage response; Occupational exposures; Shelterin complex; Telomerase; Telomere.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • DNA
  • Humans
  • Occupational Health*
  • Shelterin Complex
  • Telomere Homeostasis
  • Telomere* / genetics
  • Telomere* / metabolism
  • Telomere-Binding Proteins
  • Toxicology*

Substances

  • Shelterin Complex
  • Telomere-Binding Proteins
  • DNA