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Title 

Construction of the first compendium of chemical-genetic profiles in the fission yeast Schizosaccharomyces pombe and comparative compendium approach

Authors 

S HanM LeeH ChangM NamH O ParkY S KwakHye Jeong HaD KimS O HwangK L HoeDong Uk Kim

Publisher 

Elsevier

Issue Date 

2013

Citation 

Biochemical and Biophysical Research Communications, vol. 436, no. 4, pp. 613-618

Keywords 

Budding yeastChemical-genetic profileDrug-induced haploinsufficiencyFission yeast

Abstract 

Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defect measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at http://pombe.kaist.ac.kr/compendium.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2013.05.138

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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