A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase

Lai Hong Wong, Asier Unciti-Broceta, Michaela Spitzer, Rachel White, Mike Tyers, Lea Harrington*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Telomerase comprises a reverse transcriptase and an internal RNA template that maintains telomeres in many eukaryotes, and it is a well-validated cancer target. However, there is a dearth of small molecules with efficacy against human telomerase in vivo. We developed a surrogate yeast high-throughput assay to identify human telomerase inhibitors. The reversibility of growth arrest induced by active human telomerase was assessed against a library of 678 compounds preselected for bioactivity in S. cerevisiae. Four of eight compounds identified reproducibly restored growth to strains expressing active human telomerase, and three of these four compounds also specifically inhibited purified human telomerase in vitro. These compounds represent probes for human telomerase function, and potential entry points for development of lead compounds against telomerase-positive cancers.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalChemistry and Biology
Volume20
Issue number3
DOIs
Publication statusPublished - 21 Mar 2013

Keywords / Materials (for Non-textual outputs)

  • VIVO
  • IN-VITRO
  • RNA
  • REGIONS
  • RECONSTITUTION
  • GRN163L
  • BIBR1532
  • DAMAGE
  • SACCHAROMYCES-CEREVISIAE
  • CANCER-CELLS

Fingerprint

Dive into the research topics of 'A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase'. Together they form a unique fingerprint.

Cite this