Analysis of telomerase processivity: mechanistic similarity to HIV-1 reverse transcriptase and role in telomere maintenance

Mol Cell. 2001 Jun;7(6):1201-11. doi: 10.1016/s1097-2765(01)00268-4.

Abstract

The key protein subunit of the telomerase complex, known as TERT, possesses a reverse transcriptase (RT)-like domain that is conserved in enzymes encoded by retroviruses and retroelements. Structural and functional analysis of HIV-1 RT suggests that RT processivity is governed, in part, by the conserved motif C, motif E, and a C-terminal domain. Mutations in analogous regions of the yeast TERT were found to have anticipated effects on telomerase processivity in vitro, suggesting a great deal of mechanistic and structural similarity between TERT and retroviral RTs, and a similarity that goes beyond the homologous domain. A close correlation was uncovered between telomerase processivity and telomere length in vivo, suggesting that enzyme processivity is a limiting factor for telomere maintenance.

Publication types

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

MeSH terms

  • Catalytic Domain
  • DNA-Binding Proteins
  • HIV Reverse Transcriptase / metabolism*
  • In Vitro Techniques
  • Molecular Sequence Data
  • Mutagenesis
  • RNA
  • Sequence Homology, Amino Acid
  • Telomerase / metabolism*
  • Telomere / enzymology*
  • Yeasts

Substances

  • DNA-Binding Proteins
  • RNA primers
  • telomerase RNA
  • RNA
  • HIV Reverse Transcriptase
  • Telomerase