C-terminal regions of the human telomerase catalytic subunit essential for in vivo enzyme activity.

Published

Journal Article

Most human cancer cells are thought to acquire the ability to divide beyond the capacity of normal somatic cells through illegitimately activating the gene hTERT, which encodes the catalytic subunit of telomerase. While telomerase reverse transcriptase (TERT) is conserved in most eukaryotes, mounting evidence suggests that the C terminus of the human protein may have functions unique to higher eukaryotes. To search for domains responsible for such functions, we assayed a panel of tandem substitution mutations encompassing this region of human TERT for in vitro and in vivo functionality. We found four clusters of mutations that inactivated the biochemical and biological functions of telomerase, separated by mutations that had little or no effect on enzyme activity. We also identified a region where mutations generate catalytically active but biologically inert proteins. This C-terminal region that dissociates activities of telomerase (C-DAT) does not appear to be involved in nuclear localization or protein multimerization. Instead, it appears that the C-DAT region is involved in a step of in vivo telomere synthesis after the assembly of a catalytically active enzyme. Intriguingly, all of the described regions reside in a portion of TERT that is dispensable for cellular viability in yeast, arguing for a divergent role of the C terminus in higher eukaryotes.

Full Text

Duke Authors

Cited Authors

  • Banik, SSR; Guo, C; Smith, AC; Margolis, SS; Richardson, DA; Tirado, CA; Counter, CM

Published Date

  • September 2002

Published In

Volume / Issue

  • 22 / 17

Start / End Page

  • 6234 - 6246

PubMed ID

  • 12167716

Pubmed Central ID

  • 12167716

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.22.17.6234-6246.2002

Language

  • eng

Conference Location

  • United States