A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase

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-throughpu...

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Main Authors:	Wong, Lai Hong, Unciti-Broceta, Asier, Spitzer, Michaela, White, Rachel, Tyers, Mike, Harrington, Lea
Format:	Online
Language:	English
Published:	Elsevier 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650558/

id	pubmed-3650558
recordtype	oai_dc
spelling	pubmed-36505582013-05-13 A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase Wong, Lai Hong Unciti-Broceta, Asier Spitzer, Michaela White, Rachel Tyers, Mike Harrington, Lea Brief Communication 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. Elsevier 2013-03-21 /pmc/articles/PMC3650558/ /pubmed/23521791 http://dx.doi.org/10.1016/j.chembiol.2012.12.008 Text en © 2013 Elsevier Ltd. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wong, Lai Hong Unciti-Broceta, Asier Spitzer, Michaela White, Rachel Tyers, Mike Harrington, Lea
spellingShingle	Wong, Lai Hong Unciti-Broceta, Asier Spitzer, Michaela White, Rachel Tyers, Mike Harrington, Lea A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase
author_facet	Wong, Lai Hong Unciti-Broceta, Asier Spitzer, Michaela White, Rachel Tyers, Mike Harrington, Lea
author_sort	Wong, Lai Hong
title	A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase
title_short	A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase
title_full	A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase
title_fullStr	A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase
title_full_unstemmed	A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase
title_sort	yeast chemical genetic screen identifies inhibitors of human telomerase
description	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.
publisher	Elsevier
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650558/
_version_	1611976814299709440

A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase

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