Genetics, Vol. 166, 1215-1227, March 2004, Copyright © 2004

Genetic Interactions of DST1 in Saccharomyces cerevisiae Suggest a Role of TFIIS in the Initiation-Elongation Transition

Francisco Malagona, Amy H. Tongb,c, Brenda K. Shafera, and Jeffrey N. Stratherna
a Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702,
b Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
c Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada

Corresponding author: Jeffrey N. Strathern, Bldg. 539, Rm. 151, P.O. Box B, Frederick, MD 21702-1201., strather{at}ncifcrf.gov (E-mail)

Communicating editor: F. WINSTON

TFIIS promotes the intrinsic ability of RNA polymerase II to cleave the 3'-end of the newly synthesized RNA. This stimulatory activity of TFIIS, which is dependent upon Rpb9, facilitates the resumption of transcription elongation when the polymerase stalls or arrests. While TFIIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability. In this work we used a genetic approach to increase our knowledge of the role of TFIIS in vivo. We showed that: (1) dst1 and rpb9 mutants have a synthetic growth defective phenotype when combined with fyv4, gim5, htz1, yal011w, ybr231c, soh1, vps71, and vps72 mutants that is exacerbated during germination or at high salt concentrations; (2) TFIIS and Rpb9 are essential when the cells are challenged with microtubule-destabilizing drugs; (3) among the SDO (synthetic with Dst one), SOH1 shows the strongest genetic interaction with DST1; (4) the presence of multiple copies of TAF14, SUA7, GAL11, RTS1, and TYS1 alleviate the growth phenotype of dst1 soh1 mutants; and (5) SRB5 and SIN4 genetically interact with DST1. We propose that TFIIS is required under stress conditions and that TFIIS is important for the transition between initiation and elongation in vivo.




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