The conserved Est1 protein stimulates telomerase DNA extension activity

Diane C. DeZwaan, Brian C. Freeman

Research output: Contribution to journalArticle

Abstract

The first telomerase cofactor identified was the budding yeast protein Est1, which is conserved through humans. While it is evident that Est1 is required for telomere DNA maintenance, understanding its mechanistic contributions to telomerase regulation has been limited. In vitro, the primary effect of Est1 is to activate telomerase-mediated DNA extension. Although Est1 displayed specific DNA and RNA binding, neither activity contributed significantly to telomerase stimulation. Rather Est1 mediated telomerase upregulation through direct contacts with the reverse transcriptase subunit. In addition to intrinsic Est1 functions, we found that Est1 cooperatively activated telomerase in conjunction with Cdc13 and that the combinatorial effect was dependent upon a known salt-bridge interaction between Est1 (K444) and Cdc13 (E252). Our studies provide insights into the molecular events used to control the enzymatic activity of the telomerase holoenzyme.

Original languageEnglish (US)
Pages (from-to)17337-17342
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number41
DOIs
StatePublished - Oct 13 2009

Keywords

  • Telomerase regulation
  • Telomere biology

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'The conserved Est1 protein stimulates telomerase DNA extension activity'. Together they form a unique fingerprint.

  • Cite this