Article

 

Many Disease-Associated Variants of hTERT Retain High Telomerase Enzymatic Activity Öffentlichkeit Deposited

Herunterladbarer Inhalt

PDF Herunterladen
https://scholar.colorado.edu/concern/articles/cz30pt58f
Abstract
  • Mutations in the gene for telomerase reverse transcriptase (hTERT) are associated with diseases including dyskeratosis congenita, aplastic anemia, pulmonary fibrosis and cancer. Understanding the molecular basis of these telomerase-associated diseases requires dependable quantitative measurements of telomerase enzyme activity. Furthermore, recent findings that the human POT1-TPP1 chromosome end-binding protein complex stimulates telomerase activity and processivity provide incentive for testing variant telomerases in the presence of these factors. In the present work, we compare multiple disease-associated hTERT variants reconstituted with the RNA subunit hTR in two systems (rabbit reticulocyte lysates and human cell lines) with respect to telomerase enzymatic activity, processivity and activation by telomere proteins. Surprisingly, many of the previously reported disease-associated hTERTalleles give near-normal telomerase enzyme activity. It is possible that a small deficit in telomerase activity is sufficient to cause telomere shortening over many years. Alternatively, mutations may perturb functions such as the recruitment of telomerase to telomeres, which are essential in vivo but not revealed by simple enzyme assays.

Creator
Date Issued
  • 2013-07-03
Academic Affiliation
Journal Title
Journal Issue/Number
  • 19
Journal Volume
  • 41
File Extent
  • 8969-8978
Zuletzt geändert
  • 2020-01-08
Resource Type
Urheberrechts-Erklärung
DOI
  • 10.1093/nar/gkt653
Language

Beziehungen

In Collection:

Artikel