1. Biochemistry and Chemical Biology
  2. Cell Biology
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Identification of human TERT elements necessary for telomerase recruitment to telomeres

  1. Jens C Schmidt
  2. Andrew B Dalby
  3. Thomas R Cech  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Colorado Boulder, United States
Research Article
  • Cited 54
  • Views 3,597
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Cite this article as: eLife 2014;3:e03563 doi: 10.7554/eLife.03563

Abstract

Human chromosomes terminate in telomeres, repetitive DNA sequences bound by the shelterin complex. Shelterin protects chromosome ends, prevents recognition by the DNA damage machinery, and recruits telomerase. A patch of amino acids, termed the TEL-patch, on the OB-fold domain of the shelterin component TPP1 is essential to recruit telomerase to telomeres. In contrast, the site on telomerase that interacts with the TPP1 OB-fold is not well defined. Here we identify separation-of-function mutations in the TEN-domain of human telomerase reverse transcriptase (hTERT) that disrupt the interaction of telomerase with TPP1 in vivo and in vitro but have very little effect on the catalytic activity of telomerase. Suppression of a TEN-domain mutation with a compensatory charge-swap mutation in the TEL-patch indicates that their association is direct. Our findings define the interaction interface required for telomerase recruitment to telomeres, an important step towards developing modulators of this interaction as therapeutics for human disease.

Article and author information

Author details

  1. Jens C Schmidt

    Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Andrew B Dalby

    Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas R Cech

    Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, United States
    For correspondence
    thomas.cech@Colorado.EDU
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Carol Greider, Johns Hopkins University, United States

Publication history

  1. Received: June 3, 2014
  2. Accepted: October 1, 2014
  3. Accepted Manuscript published: October 1, 2014 (version 1)
  4. Version of Record published: November 3, 2014 (version 2)

Copyright

© 2014, Schmidt et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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