Telomerase Mechanism of Telomere Synthesis

Annu Rev Biochem. 2017 Jun 20;86:439-460. doi: 10.1146/annurev-biochem-061516-045019. Epub 2017 Jan 30.

Abstract

Telomerase is the essential reverse transcriptase required for linear chromosome maintenance in most eukaryotes. Telomerase supplements the tandem array of simple-sequence repeats at chromosome ends to compensate for the DNA erosion inherent in genome replication. The template for telomerase reverse transcriptase is within the RNA subunit of the ribonucleoprotein complex, which in cells contains additional telomerase holoenzyme proteins that assemble the active ribonucleoprotein and promote its function at telomeres. Telomerase is distinct among polymerases in its reiterative reuse of an internal template. The template is precisely defined, processively copied, and regenerated by release of single-stranded product DNA. New specificities of nucleic acid handling that underlie the catalytic cycle of repeat synthesis derive from both active site specialization and new motif elaborations in protein and RNA subunits. Studies of telomerase provide unique insights into cellular requirements for genome stability, tissue renewal, and tumorigenesis as well as new perspectives on dynamic ribonucleoprotein machines.

Keywords: DNA replication; reverse transcriptase; ribonucleoprotein biogenesis; telomere.

Publication types

  • Review

MeSH terms

  • Animals
  • Catalytic Domain
  • DNA Replication*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism*
  • Gene Expression Regulation
  • Humans
  • Microsatellite Repeats
  • Nucleic Acid Conformation
  • Oxytricha / genetics
  • Oxytricha / metabolism
  • RNA / genetics
  • RNA / metabolism*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / chemistry
  • Telomere / enzymology*
  • Tetrahymena thermophila / genetics
  • Tetrahymena thermophila / metabolism

Substances

  • DNA, Single-Stranded
  • Ribonucleoproteins
  • RNA
  • Telomerase