Telomeres and telomerase: three decades of progress

Nat Rev Genet. 2019 May;20(5):299-309. doi: 10.1038/s41576-019-0099-1.

Abstract

Many recent advances have emerged in the telomere and telomerase fields. This Timeline article highlights the key advances that have expanded our views on the mechanistic underpinnings of telomeres and telomerase and their roles in ageing and disease. Three decades ago, the classic view was that telomeres protected the natural ends of linear chromosomes and that telomerase was a specific telomere-terminal transferase necessary for the replication of chromosome ends in single-celled organisms. While this concept is still correct, many diverse fields associated with telomeres and telomerase have substantially matured. These areas include the discovery of most of the key molecular components of telomerase, implications for limits to cellular replication, identification and characterization of human genetic disorders that result in premature telomere shortening, the concept that inhibiting telomerase might be a successful therapeutic strategy and roles for telomeres in regulating gene expression. We discuss progress in these areas and conclude with challenges and unanswered questions in the field.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / metabolism
  • Abnormalities, Multiple / pathology
  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • Gene Expression Regulation
  • Genomics / history*
  • Genomics / methods
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Molecular Chaperones
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Progeria / genetics
  • Progeria / metabolism
  • Progeria / pathology
  • Ribonucleoproteins, Small Nuclear / genetics
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Ribonucleoproteins, Small Nucleolar / genetics
  • Ribonucleoproteins, Small Nucleolar / metabolism
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Telomere / chemistry*
  • Telomere / metabolism
  • Telomere Homeostasis
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • DKC1 protein, human
  • Molecular Chaperones
  • NHP2 protein, human
  • NOP10 protein, human
  • Nuclear Proteins
  • Ribonucleoproteins, Small Nuclear
  • Ribonucleoproteins, Small Nucleolar
  • Telomere-Binding Proteins
  • shelterin, human
  • DNA
  • TERT protein, human
  • Telomerase
  • WRAP53 protein, human