The Telomerase Reverse Transcriptase Is Limiting and Necessary for Telomerase Function in Vivo

Curr Biol. 2000 Nov 16;10(22):1459-62. doi: 10.1016/s0960-9822(00)00805-8.

Abstract

Mammalian telomerase is essential for the maintenance of telomere length [1-5]. Its catalytic core comprises a reverse transcriptase component (TERT) and an RNA component. While the biochemical role of mammalian TERT is well established [6-11], it is unknown whether it is sufficient for telomere-length maintenance, chromosome stability or other cellular processes. Cells from mice in which the mTert gene had been disrupted showed progressive loss of telomere DNA, a phenotype similar to cells in which the gene encoding the telomerase RNA component (mTR) has been disrupted [1,12]. On prolonged growth, mTert-deficient embryonic stem (ES) cells exhibited genomic instability, aneuploidy and telomeric fusions. ES cells heterozygous for the mTert disruption also showed telomere attrition, a phenotype that differs from heterozygous mTR cells [12]. Thus, telomere maintenance in mammals is carried out by a single, limiting TERT.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins
  • Gene Targeting
  • Mice
  • RNA*
  • Telomerase / genetics
  • Telomerase / metabolism
  • Telomerase / physiology*
  • Telomere / physiology*

Substances

  • DNA-Binding Proteins
  • telomerase RNA
  • RNA
  • Telomerase
  • Tert protein, mouse