Large-scale mutagenesis and functional genomics in yeast

Abstract. One of the major goals for the post-genome era is determining of the function of proteins predicted in the genome sequence. In many organisms functional assignments have been the results of comparative sequencing, proteomics or expression profiling. In the yeast, Saccharomyces cerevisiae, however, the functional role of a gene can be tested directly by disrupting the gene and examining the phenotype of the mutant. Because precise targeted deletions can be easily constructed, it is also possible to systematically delete every gene in the genome. Here we describe recent progress in yeast genome-wide mutagenesis programs and the results produced from analyzing the mutants created by them.

[1]  M. Boguski,et al.  A Survey of Human Disease Gene Counterparts in the Drosophila Genome , 2000, The Journal of cell biology.

[2]  Ronald W. Davis,et al.  Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. , 1999, Science.

[3]  M. Snyder,et al.  A genomic study of the bipolar bud site selection pattern in Saccharomyces cerevisiae. , 2001, Molecular biology of the cell.

[4]  Elizabeth A. Winzeler,et al.  Genomic profiling of drug sensitivities via induced haploinsufficiency , 1999, Nature Genetics.

[5]  J. Boeke,et al.  Small open reading frames: beautiful needles in the haystack. , 1997, Genome research.

[6]  G. Chua,et al.  Insertional mutagenesis based on illegitimate recombination in Schizosaccharomyces pombe. , 2000, Nucleic acids research.

[7]  Kei-Hoi Cheung,et al.  An integrated approach for finding overlooked genes in yeast , 2002, Nature Biotechnology.

[8]  D. Botstein,et al.  Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Seth Sadis,et al.  Complementary whole-genome technologies reveal the cellular response to proteasome inhibition by PS-341 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Gary D Bader,et al.  Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants , 2001, Science.

[11]  Kei-Hoi Cheung,et al.  Large-scale analysis of the yeast genome by transposon tagging and gene disruption , 1999, Nature.

[12]  M. Johnston,et al.  The yeast genome: on the road to the Golden Age. , 2000, Current opinion in genetics & development.

[13]  J. Boeke,et al.  A DNA Microarray-Based Genetic Screen for Nonhomologous End-Joining Mutants in Saccharomyces cerevisiae , 2001, Science.

[14]  L. Hartwell,et al.  Integrating genetic approaches into the discovery of anticancer drugs. , 1997, Science.

[15]  M. Boguski,et al.  Genome cross-referencing and XREFdb: Implications for the identification and analysis of genes mutated in human disease , 1997, Nature Genetics.

[16]  A. Goffeau.  Four years of post‐genomic life with 6000 yeast genes , 2000, FEBS letters.

[17]  T. Hughes,et al.  Identification of the single-strand telomeric DNA binding domain of the Saccharomyces cerevisiae Cdc13 protein. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  K. Ito,et al.  Identification of genes required for growth under ethanol stress using transposon mutagenesis in Saccharomyces cerevisiae , 2001, Molecular Genetics and Genomics.

[19]  R. Rothstein.  One-step gene disruption in yeast. , 1983, Methods in enzymology.

[20]  Robert E. Johnson,et al.  Requirement of the Yeast MSH3 and MSH6 Genes for MSH2-dependent Genomic Stability (*) , 1996, The Journal of Biological Chemistry.

[21]  B. Stockwell.  Chemical genetics: ligand-based discovery of gene function , 2000, Nature Reviews Genetics.

[22]  Ronald W. Davis,et al.  A genome-wide screen in Saccharomyces cerevisiae for genes affecting UV radiation sensitivity , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  B. Barrell,et al.  Life with 6000 Genes , 1996, Science.

[24]  J. Beggs.  Transformation of yeast by a replicating hybrid plasmid , 1978, Nature.

[25]  M. Resnick,et al.  Genes required for ionizing radiation resistance in yeast , 2001, Nature Genetics.

[26]  M. Snyder,et al.  Emerging technologies in yeast genomics , 2001, Nature Reviews Genetics.

[27]  M. Johnston,et al.  A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR). , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Ronald W. Davis,et al.  Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar–coding strategy , 1996, Nature Genetics.

[29]  Kei-Hoi Cheung,et al.  The TRIPLES database: a community resource for yeast molecular biology , 2002, Nucleic Acids Res..

[30]  Hongyue Dai,et al.  Widespread aneuploidy revealed by DNA microarray expression profiling , 2000, Nature Genetics.

[31]  D Botstein,et al.  Suppressors of yeast actin mutations. , 1989, Genetics.

[32]  James I. Garrels,et al.  The Yeast Proteome Database (YPD): a model for the organization and presentation of genome-wide functional data , 1999, Nucleic Acids Res..

[33]  C. S. Hoffman,et al.  Mutagenesis and gene cloning in Schizosaccharomyces pombe using nonhomologous plasmid integration and rescue. , 2000, BioTechniques.