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Systematic genome instability screens in yeast and their potential relevance to cancer.


ABSTRACT: To systematically identify genes that maintain genome structure, yeast knockout mutants were examined by using three assays that followed marker inheritance in different chromosomal contexts. These screens identified 130 null mutant strains exhibiting chromosome instability (CIN) phenotypes. Differences in both phenotype severity and assay specificity were observed. The results demonstrate the advantages of using complementary assays to comprehensively identify genome maintenance determinants. Genome structure was important in determining the spectrum of gene and pathway mutations causing a chromosome instability phenotype. Protein similarity identified homologues in other species, including human genes with relevance to cancer. This extensive genome instability catalog can be combined with emerging genetic interaction data from yeast to support the identification of candidate targets for therapeutic elimination of chromosomally unstable cancer cells by selective cell killing.

SUBMITTER: Yuen KW 

PROVIDER: S-EPMC1820685 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Systematic genome instability screens in yeast and their potential relevance to cancer.

Yuen Karen W Y KW   Warren Cheryl D CD   Chen Ou O   Kwok Teresa T   Hieter Phil P   Spencer Forrest A FA  

Proceedings of the National Academy of Sciences of the United States of America 20070228 10


To systematically identify genes that maintain genome structure, yeast knockout mutants were examined by using three assays that followed marker inheritance in different chromosomal contexts. These screens identified 130 null mutant strains exhibiting chromosome instability (CIN) phenotypes. Differences in both phenotype severity and assay specificity were observed. The results demonstrate the advantages of using complementary assays to comprehensively identify genome maintenance determinants. G  ...[more]

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