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Developmental Therapeutics Program (DTP)
Last Updated: 08/18/15

Experimental Design

The compounds were screened against a panel of Saccharomyces cerevisiae mutant strains that have alterations in DNA damage repair or cell cycle control. All screening was performed by the Seattle Project at the Fred Hutchinson Cancer Research Center in Seattle, Washington under the direction of Dr. Julian Simon. A brief description of the mutants can be found below. More detailed information on these genes can be found at the Saccharomyces Genome Database and at the MIPS Comprehensive Yeast Genome Database.

Strain list

The Tests:

Stage0 experiments were performed at a single dose, 50 microM, in duplicate. Stage1 experiments were performed at two doses, 5 microM and 50 microM, in duplicate. The data in the tables are presented as growth inhibition of the yeast strain exposed to the compound relative to the growth of the yeast strain treated with solvent only.

In Stage0 and Stage1 experiments 6 yeast strains were used, containing 1 or 2 mutations of interest. All 6 strains also were mutant for 3 genes (erg6, pdr1 & pdr3) that increase yeast’s sensitivity to drugs. 3 strains contained single mutations in genes of interest: rad50, mec2 or bub3. 3 strains were doubly mutant: rad18 + mlh1, sgs1 + mgt1 and rad14 + CLN2oe.

Stage2 experiments were performed at 5 doses, in duplicate. Doses used were 100 microM, 33 microM, 11 microM, 3.7 microM and 1.2 microM. The data are derived from the fraction of growth of the yeast strain exposed to the compound relative to the growth of the same yeast strain treated with solvent only. In Stage2 experiments “wild-type” controls have been included. “wt1” serves as the control for the bub3, CLN2oe, mec2, rad14, rad18, rad50 and rad52 strains. “wt2” serves as the control for the mgt1, mlh1, rad50EPP+ and sgs1 strains.

In Stage2 experiments the strains were each mutant for a single target gene, as well as for 3 genes (erg6, pdr1 & pdr3) that increase yeast's sensitivity to drugs.

The Genes:

Click on the gene name to find out more about this gene from the Saccharomyces Genome Database. If a human homolog has been identified, click on the link for more information about human disease associations from OMIM. There is also a link to compounds that inhibited each strain in Stage2 tests. This will return a table with compounds that inhibited the growth of the given strain by at least 70% at one or more of the tested doses. These tables include compounds specifically toxic to a given strain (e.g. only bub3 inhibited for at least one of the tested doses) and compounds that are somewhat specific (e.g. bub3 plus CLN2oe inhibited for at least one dose).

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Email questions to: Susan Holbeck [ holbecks@mail.nih.gov ]