Telomeres in toxicology: Occupational health

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. Therefo...

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Published inPharmacology & therapeutics (Oxford) Vol. 220; p. 107742
Main Authors Shoeb, Mohammad, Meier, Helen C.S., Antonini, James M.
Format Journal Article
LanguageEnglish
Published England Elsevier Inc 01.04.2021
Subjects
DNA
DNA damage
DNA damage response
Humans
Occupational exposures
Occupational Health
Shelterin Complex
Telomerase
Telomere
Telomere - genetics
Telomere - metabolism
Telomere Homeostasis
Telomere-Binding Proteins
Toxicology
DNA damage response
TERC
DNA damage
ALT
Telomere
Shelterin complex
Occupational exposures
TRF1 and TRF2
DDR
TERT
RAP1
POT1
TPP1
ATM
Telomerase
ssDNA
dsDNA
TIN2
ATR
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Summary: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.
ISSN:0163-7258
1879-016X
DOI:10.1016/j.pharmthera.2020.107742