REFERENCES 33 Baumann, G., Zenke, G., Wenger, R., Hiestand, P., Quesniaux, V., Andersen, E. and Schreier, M. H. (1992). Molecular mechanisms of immunosuppression. J. Autoimmun. 5, 67–72. Bjornsti, M. A., Knab, A. M. and Benedetti, P. (1994). Yeast Saccharomyces cerevisiae as a model system to study the cytotoxic activity of the antitumor drug camptothec<strong>in</strong>. Cancer Chemother. Pharmacol. 34, S1–S5. Boles, E., Liebetrau, W., Hofmann, M. and Zimmermann, F. K. (1994). A family of hexosephosphate mutases <strong>in</strong> Saccharomyces cerevisiae. Eur. J. Biochem. 220, 83–96. Bossard, M. J., Bergsma, D. J., Brandt, M., Livi, G. P., Eng, W. K., Johnson, R. K. and Levy, M. A. (1994). Catalytic and ligand b<strong>in</strong>d<strong>in</strong>g properties of the FK506 b<strong>in</strong>d<strong>in</strong>g prote<strong>in</strong> FKBP12: effects of the s<strong>in</strong>gle am<strong>in</strong>o acid substitution of Tyr82 to Leu. Biochem. J. 297, 365–372. Botste<strong>in</strong>, D., Chervitz, S. A. and Cherry, J. M. (1997). Yeast as a model organism. Science 277, 1259–1260. Burchett, S. A., Scott, A., Errede, B. and Dohlman, H. G. (2001). Identification of novel pheromone-response regulators through systematic overexpression of 120 prote<strong>in</strong> k<strong>in</strong>ases <strong>in</strong> yeast. J. Biol. Chem. 276, 26472–26478. Cafferkey, R., Young, P. R., McLaughl<strong>in</strong>, M. M., Bergsma, D. J., Kolt<strong>in</strong>, Y., Sathe, G. M., Faucette, L., et al. (1993). Dom<strong>in</strong>ant missense mutations <strong>in</strong> a novel yeast prote<strong>in</strong> related to mammalian phosphatidyl<strong>in</strong>ositol 3-k<strong>in</strong>ase and VPS34 abrogate rapamyc<strong>in</strong> cytotoxicity. Mol. Cell. Biol. 13, 6012–6023. Cafferkey, R., McLaughl<strong>in</strong>, M. M., Young, P. R., Johnson, R. K. and Livi, G. P. (1994). Yeast TOR (DRR) prote<strong>in</strong>s: am<strong>in</strong>o-acid sequence alignment and identification of structural motifs. Gene 141, 133–136. Cagney, G., Uetz, P. and Fields, S. (2001). Two-hybrid analysis of the Saccharomyces cerevisiae 26S proteasome. Physiol. Genom. 7, 27–34. Cardenas, M. E., Lorenz, M., Hemenway, C. and Heitman, J. (1994). Yeast as model T cells. Perspect. <strong>Drug</strong> Discov. Design 2, 103–126. Chan, T. F., Carvalho, J., Riles, L. and Zheng, X. F. (2000). A chemical genomics approach toward understand<strong>in</strong>g the global functions of the target of rapamyc<strong>in</strong> prote<strong>in</strong> (TOR). Proc. Natl. Acad. Sci. USA 97, 13227–13232. Chaturvedi, P., Eng, W. K., Zhu, Y., Mattern, M. R., Mishra, R., Hurle, M. R., Zhang, X., et al. (1999). Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpo<strong>in</strong>t pathway. Oncogene 18, 4047–4054. Chervitz, S. A., Arav<strong>in</strong>d, L., Sherlock, G., Ball, C. A., Koon<strong>in</strong>, E. V., Dwight, S. S., Harris, M. A., et al. (1998). Comparison of the complete prote<strong>in</strong> sets of worm and yeast: orthology and divergence. Science 282, 2022–2028. Clow, A., Greenhalf, W. and Chaudhuri, B. (1998). Under respiratory growth conditions, Bcl-x(L) and Bcl-2 are unable to overcome yeast cell death triggered by a mutant Bax prote<strong>in</strong> lack<strong>in</strong>g the membrane anchor. Eur. J. Biochem. 258, 19–28. Costanzo, M. C., Crawford, M. E., Hirschman, J. E., Kranz, J. E., Olsen, P., Robertson, L. S., Skrzypek, M. S., et al. (2001). YPD, PombePD and WormPD: model organism volumes of the BioKnowledge library, an <strong>in</strong>tegrated resource for prote<strong>in</strong> <strong>in</strong>formation. Nucleic Acids Res. 29, 75–79. DiBello, P. R., Garrison, T. R., Apanovitch, D. M., Hoffman, G., Shuey, D. J., Mason, K., Cockett, M. I., et al. (1998). Selective uncoupl<strong>in</strong>g of RGS action by a s<strong>in</strong>gle po<strong>in</strong>t mutation <strong>in</strong> the G prote<strong>in</strong> alpha-subunit. J. Biol. Chem. 273, 5780–5784. Dimmer, K. S., Fritz, S., Fuchs, F., Messerschmitt, M., We<strong>in</strong>bach, N., Neupert, W. and Westermann, B. (2002). Genetic basis of mitochondrial function and morphology <strong>in</strong> Saccharomyces cerevisiae. Mol. Biol. Cell. 13, 847–853.
34 GROWING YEAST FOR FUN AND PROFIT Dimster-Denk, D., R<strong>in</strong>e, J., Phillips, J., Scherer, S., Cundiff, P., DeBord, K., Gilliland, D., et al. (1999). Comprehensive evaluation of isoprenoid biosynthesis regulation <strong>in</strong> Saccharomyces cerevisiae utiliz<strong>in</strong>g the Genome Reporter Matrix. J. Lipid Res. 40, 850– 860. Dohlman, H. G. (2002). G prote<strong>in</strong>s and pheromone signal<strong>in</strong>g. Annu. Rev. Physiol. 64, 129– 152. Dowell, S. J., Bishop, A. L., Dyos, S. L., Brown, A. J. and Whiteway, M. S. (1998). Mapp<strong>in</strong>g of a yeast G prote<strong>in</strong> betagamma signal<strong>in</strong>g <strong>in</strong>teraction. Genetics 150, 1407–1417. Drosos, A. A. (2002). Newer immunosuppressive drugs: their potential role <strong>in</strong> rheumatoid arthritis therapy. <strong>Drug</strong>s 62, 891–907. Duan, H., Wang, Y., Aviram, M., Swaroop, M., Loo, J. A., Bian, J., Tian, Y., et al. (1999). SAG, a novel z<strong>in</strong>c RING f<strong>in</strong>ger prote<strong>in</strong> that protects cells from apoptosis <strong>in</strong>duced by redox agents. Mol. Cell. Biol. 19, 3145–3155. Dumont, F. J., Staruch, M. J., Koprak, S. L., Mel<strong>in</strong>o, M. R. and Sigal, N. H. (1990). Dist<strong>in</strong>ct mechanisms of suppression of mur<strong>in</strong>e T cell activation by the related macrolides FK-506 and rapamyc<strong>in</strong>. J. Immunol. 144, 251–258. Dwight, S. S., Harris, M. A., Dol<strong>in</strong>ski, K., Ball, C. A., B<strong>in</strong>kley, G., Christie, K. R., Fisk, D. G., et al. (2002). Saccharomyces Genome Database (SGD) provides secondary gene annotation us<strong>in</strong>g the Gene Ontology (GO). Nucleic Acids Res. 30, 69–72. Flem<strong>in</strong>g, J. A., Lightcap, E. S., Sadis, S., Thoroddsen, V., Bulawa, C. E. and Blackman, R. K. (2002). Complementary whole-genome technologies reveal the cellular response to proteasome <strong>in</strong>hibition by PS-341. Proc. Natl. Acad. Sci. USA 99, 1461–1466. Flores, A., Briand, J. F., Gadal, O., Andrau, J. C., Rubbi, L., Van Mullem, V., Boschiero, C., et al. (1999). A prote<strong>in</strong>–prote<strong>in</strong> <strong>in</strong>teraction map of yeast RNA polymerase III. Proc. Natl. Acad. Sci. USA 96, 7815–7820. Frohlich, K. U. and Madeo, F. (2000). Apoptosis <strong>in</strong> yeast – a monocellular organism exhibits altruistic behaviour. FEBS Lett. 473, 6–9. Fromont-Rac<strong>in</strong>e, M., Ra<strong>in</strong>, J. C. and Legra<strong>in</strong>, P. (1997). Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens [see comments]. Nat. Genet. 16, 277–282. Furet, P., Imbach, P., Furst, P., Lang, M., Noorani, M., Zimmermann, J. and Garcia- Echeverria, C. (2001). <strong>Model</strong><strong>in</strong>g of the b<strong>in</strong>d<strong>in</strong>g mode of a non-covalent <strong>in</strong>hibitor of the 20S proteasome. Application to structure-based analogue design. Bioorg. Med. Chem. Lett. 11, 1321–1324. Gav<strong>in</strong>, A. C., Bosche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., et al. (2002). Functional organization of the yeast proteome by systematic analysis of prote<strong>in</strong> complexes. Nature 415, 141–147. Giaever, G., Shoemaker, D. D., Jones, T. W., Liang, H., W<strong>in</strong>zeler, E. A., Astromoff, A. and Davis, R. W. (1999). Genomic profil<strong>in</strong>g of drug sensitivities via <strong>in</strong>duced haplo<strong>in</strong>sufficiency. Nat. Genet. 21, 278–283. Giaever, G., Chu, A. M., Ni, L., Connelly, C., Riles, L., Veronneau, S., Dow, S., et al. (2002). Functional profil<strong>in</strong>g of the Saccharomyces cerevisiae genome. Nature 418, 387–391. Goffeau, A., Barrell, B. G., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., Galibert, F., et al. (1996). Life with 6000 genes [see comments]. Science 274, 546, 563–547. Greenhalf, W., Stephan, C. and Chaudhuri, B. (1996). Role of mitochondria and Cterm<strong>in</strong>al membrane anchor of Bcl-2 <strong>in</strong> Bax <strong>in</strong>duced growth arrest and mortality <strong>in</strong> Saccharomyces cerevisiae. FEBS Lett. 380, 169–175. Greenhalf, W., Lee, J. and Chaudhuri, B. (1999). A selection system for human apoptosis <strong>in</strong>hibitors us<strong>in</strong>g yeast. Yeast 15, 1307–1321.
- Page 1 and 2: Model Organisms in Drug Discovery M
- Page 3 and 4: Copyright u 2003 John Wiley & Sons
- Page 5 and 6: Contents List of contributors .....
- Page 7 and 8: CONTENTS ix 7 Genetics and Genomics
- Page 9 and 10: List of Contributors Hector Beltran
- Page 11 and 12: LIST OF CONTRIBUTORS xiii Stefan Sc
- Page 13 and 14: 1 Introduction to Model Systems in
- Page 15 and 16: Organism INTEGRATING MODEL ORGANISM
- Page 17 and 18: INTEGRATING MODEL ORGANISM RESEARCH
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- Page 51 and 52: 3 Caenorhabditis elegans Functional
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- Page 55 and 56: multivulva phenotype of Ras gain-of
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- Page 59 and 60: FROM DISEASE TO TARGET 49 Figure 3.
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- Page 63 and 64: signaling pathway. The third catego
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- Page 91 and 92: 82 DROSOPHILA AS A TOOL FOR DRUG DI
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86 DROSOPHILA AS A TOOL FOR DRUG DI
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88 DROSOPHILA AS A TOOL FOR DRUG DI
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92 DROSOPHILA AS A TOOL FOR DRUG DI
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94 DROSOPHILA AS A TOOL FOR DRUG DI
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96 DROSOPHILA AS A TOOL FOR DRUG DI
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98 DROSOPHILA AS A TOOL FOR DRUG DI
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114 DROSOPHILA AS A TOOL FOR DRUG D
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116 DROSOPHILA AS A TOOL FOR DRUG D
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5 Drosophila - a Model System for T
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EVOLUTIONARY CONSERVATION OF DISEAS
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EVOLUTIONARY CONSERVATION OF DISEAS
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EVOLUTIONARY CONSERVATION OF DISEAS
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EVOLUTIONARY CONSERVATION OF DISEAS
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TARGET IDENTIFICATION/TARGET VALIDA
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TARGET IDENTIFICATION/TARGET VALIDA
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CHEMICAL GENETICS 143 acid identity
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3. A hit identifies a biologically
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about their function in a multicell
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REFERENCES 149 Han, Z. S., Enslen,
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REFERENCES 151 Rintelen, F., Stocke
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6 Mechanism of Action in Model Orga
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INTRODUCTION TO COMPOUND DEVELOPMEN
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MODEL ORGANISMS ARRIVE ON THE SCENE
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ELUCIDATING THE MECHANISM OF COMPOU
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ELUCIDATING THE MECHANISM OF COMPOU
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A CASE STUDY FOR ALZHEIMER’S DISE
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A CASE STUDY FOR ALZHEIMER’S DISE
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A CASE STUDY FOR ALZHEIMER’S DISE
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A CASE STUDY FOR ALZHEIMER’S DISE
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NEW CHEMICAL GENETIC STRATEGIES 171
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A CASE STUDY FOR INNATE IMMUNITY 17
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GLOBAL GENE EXPRESSION STUDIES IN M
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As described above, the extensive i
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REFERENCES 179 Austin, J. and Kimbl
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REFERENCES 181 Hughes, T. R., Marto
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REFERENCES 183 Sin, N., Meng, L., W
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186 GENETICS AND GENOMICS IN THE ZE
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188 GENETICS AND GENOMICS IN THE ZE
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190 GENETICS AND GENOMICS IN THE ZE
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198 GENETICS AND GENOMICS IN THE ZE
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200 GENETICS AND GENOMICS IN THE ZE
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8 Lipid Metabolism and Signaling in
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FISH AS A MODEL ORGANISM 205 genes
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LIPID METABOLISM SCREEN 207 transpo
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LIPID METABOLISM SCREEN 209 Figure
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the embryo media containing radioac
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ZEBRAFISH AS A MODEL SYSTEM 213 Fig
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ZEBRAFISH AS A MODEL SYSTEM 215 Reg
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aspirin, which has potent inhibitor
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REFERENCES 219 Chau, I. and Cunning
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REFERENCES 221 Patrono, C., Patrign
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224 CHEMICAL MUTAGENESIS IN THE MOU
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226 CHEMICAL MUTAGENESIS IN THE MOU
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228 CHEMICAL MUTAGENESIS IN THE MOU
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230 CHEMICAL MUTAGENESIS IN THE MOU
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232 CHEMICAL MUTAGENESIS IN THE MOU
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234 CHEMICAL MUTAGENESIS IN THE MOU
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236 CHEMICAL MUTAGENESIS IN THE MOU
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238 CHEMICAL MUTAGENESIS IN THE MOU
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240 CHEMICAL MUTAGENESIS IN THE MOU
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242 CHEMICAL MUTAGENESIS IN THE MOU
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244 CHEMICAL MUTAGENESIS IN THE MOU
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246 CHEMICAL MUTAGENESIS IN THE MOU
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248 CHEMICAL MUTAGENESIS IN THE MOU
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250 CHEMICAL MUTAGENESIS IN THE MOU
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252 SATURATION SCREENING OF DRUGGAB
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254 SATURATION SCREENING OF DRUGGAB
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256 SATURATION SCREENING OF DRUGGAB
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258 SATURATION SCREENING OF DRUGGAB
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260 SATURATION SCREENING OF DRUGGAB
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262 SATURATION SCREENING OF DRUGGAB
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264 SATURATION SCREENING OF DRUGGAB
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266 SATURATION SCREENING OF DRUGGAB
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268 SATURATION SCREENING OF DRUGGAB
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270 SATURATION SCREENING OF DRUGGAB
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272 SATURATION SCREENING OF DRUGGAB
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274 SATURATION SCREENING OF DRUGGAB
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276 SATURATION SCREENING OF DRUGGAB
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278 SATURATION SCREENING OF DRUGGAB
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280 INDEX bupropion 92 busulfan 143
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282 INDEX Dscam 171 dual-energy X-r
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284 INDEX L-685,818 16 lead discove
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286 INDEX protein function 19-22 pr
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288 INDEX yeast (continued) functio