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. 2001 May;158(1):145–154. doi: 10.1093/genetics/158.1.145

The Saccharomyces cerevisiae suppressor of choline sensitivity (SCS2) gene is a multicopy Suppressor of mec1 telomeric silencing defects.

R J Craven 1, T D Petes 1
PMCID: PMC1461656  PMID: 11333225

Abstract

Mec1p is a cell cycle checkpoint protein related to the ATM protein kinase family. Certain mec1 mutations or overexpression of Mec1p lead to shortened telomeres and loss of telomeric silencing. We conducted a multicopy suppressor screen for genes that suppress the loss of silencing in strains overexpressing Mec1p. We identified SCS2 (suppressor of choline sensitivity), a gene previously isolated as a suppressor of defects in inositol synthesis. Deletion of SCS2 resulted in decreased telomeric silencing, and the scs2 mutation increased the rate of cellular senescence observed for mec1-21 tel1 double mutant cells. Genetic analysis revealed that Scs2p probably acts through a different telomeric silencing pathway from that affected by Mec1p.

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Selected References

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  1. Aparicio O. M., Billington B. L., Gottschling D. E. Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae. Cell. 1991 Sep 20;66(6):1279–1287. doi: 10.1016/0092-8674(91)90049-5. [DOI] [PubMed] [Google Scholar]
  2. Boulton S. J., Jackson S. P. Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing. EMBO J. 1998 Mar 16;17(6):1819–1828. doi: 10.1093/emboj/17.6.1819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Christianson T. W., Sikorski R. S., Dante M., Shero J. H., Hieter P. Multifunctional yeast high-copy-number shuttle vectors. Gene. 1992 Jan 2;110(1):119–122. doi: 10.1016/0378-1119(92)90454-w. [DOI] [PubMed] [Google Scholar]
  4. Craven R. J., Petes T. D. Dependence of the regulation of telomere length on the type of subtelomeric repeat in the yeast Saccharomyces cerevisiae. Genetics. 1999 Aug;152(4):1531–1541. doi: 10.1093/genetics/152.4.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Craven R. J., Petes T. D. Involvement of the checkpoint protein Mec1p in silencing of gene expression at telomeres in Saccharomyces cerevisiae. Mol Cell Biol. 2000 Apr;20(7):2378–2384. doi: 10.1128/mcb.20.7.2378-2384.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dahlen M., Olsson T., Kanter-Smoler G., Ramne A., Sunnerhagen P. Regulation of telomere length by checkpoint genes in Schizosaccharomyces pombe. Mol Biol Cell. 1998 Mar;9(3):611–621. doi: 10.1091/mbc.9.3.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DeMarini D. J., Adams A. E., Fares H., De Virgilio C., Valle G., Chuang J. S., Pringle J. R. A septin-based hierarchy of proteins required for localized deposition of chitin in the Saccharomyces cerevisiae cell wall. J Cell Biol. 1997 Oct 6;139(1):75–93. doi: 10.1083/jcb.139.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dean-Johnson M., Henry S. A. Biosynthesis of inositol in yeast. Primary structure of myo-inositol-1-phosphate synthase (EC 5.5.1.4) and functional analysis of its structural gene, the INO1 locus. J Biol Chem. 1989 Jan 15;264(2):1274–1283. [PubMed] [Google Scholar]
  9. Desany B. A., Alcasabas A. A., Bachant J. B., Elledge S. J. Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway. Genes Dev. 1998 Sep 15;12(18):2956–2970. doi: 10.1101/gad.12.18.2956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gietz R. D., Sugino A. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene. 1988 Dec 30;74(2):527–534. doi: 10.1016/0378-1119(88)90185-0. [DOI] [PubMed] [Google Scholar]
  11. Gilson E., Roberge M., Giraldo R., Rhodes D., Gasser S. M. Distortion of the DNA double helix by RAP1 at silencers and multiple telomeric binding sites. J Mol Biol. 1993 May 20;231(2):293–310. doi: 10.1006/jmbi.1993.1283. [DOI] [PubMed] [Google Scholar]
  12. Gotta M., Laroche T., Formenton A., Maillet L., Scherthan H., Gasser S. M. The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae. J Cell Biol. 1996 Sep;134(6):1349–1363. doi: 10.1083/jcb.134.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gottschling D. E., Aparicio O. M., Billington B. L., Zakian V. A. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell. 1990 Nov 16;63(4):751–762. doi: 10.1016/0092-8674(90)90141-z. [DOI] [PubMed] [Google Scholar]
  14. Greenwell P. W., Kronmal S. L., Porter S. E., Gassenhuber J., Obermaier B., Petes T. D. TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene. Cell. 1995 Sep 8;82(5):823–829. doi: 10.1016/0092-8674(95)90479-4. [DOI] [PubMed] [Google Scholar]
  15. Hardy C. F., Sussel L., Shore D. A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation. Genes Dev. 1992 May;6(5):801–814. doi: 10.1101/gad.6.5.801. [DOI] [PubMed] [Google Scholar]
  16. Hecht A., Laroche T., Strahl-Bolsinger S., Gasser S. M., Grunstein M. Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Cell. 1995 Feb 24;80(4):583–592. doi: 10.1016/0092-8674(95)90512-x. [DOI] [PubMed] [Google Scholar]
  17. Hirsch J. P., Henry S. A. Expression of the Saccharomyces cerevisiae inositol-1-phosphate synthase (INO1) gene is regulated by factors that affect phospholipid synthesis. Mol Cell Biol. 1986 Oct;6(10):3320–3328. doi: 10.1128/mcb.6.10.3320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kagiwada S., Hosaka K., Murata M., Nikawa J., Takatsuki A. The Saccharomyces cerevisiae SCS2 gene product, a homolog of a synaptobrevin-associated protein, is an integral membrane protein of the endoplasmic reticulum and is required for inositol metabolism. J Bacteriol. 1998 Apr;180(7):1700–1708. doi: 10.1128/jb.180.7.1700-1708.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kyrion G., Liu K., Liu C., Lustig A. J. RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae. Genes Dev. 1993 Jul;7(7A):1146–1159. doi: 10.1101/gad.7.7a.1146. [DOI] [PubMed] [Google Scholar]
  20. Lapierre L. A., Tuma P. L., Navarre J., Goldenring J. R., Anderson J. M. VAP-33 localizes to both an intracellular vesicle population and with occludin at the tight junction. J Cell Sci. 1999 Nov;112(Pt 21):3723–3732. doi: 10.1242/jcs.112.21.3723. [DOI] [PubMed] [Google Scholar]
  21. Longhese M. P., Paciotti V., Neecke H., Lucchini G. Checkpoint proteins influence telomeric silencing and length maintenance in budding yeast. Genetics. 2000 Aug;155(4):1577–1591. doi: 10.1093/genetics/155.4.1577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Longtine M. S., McKenzie A., 3rd, Demarini D. J., Shah N. G., Wach A., Brachat A., Philippsen P., Pringle J. R. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast. 1998 Jul;14(10):953–961. doi: 10.1002/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  23. Lowndes N. F., Murguia J. R. Sensing and responding to DNA damage. Curr Opin Genet Dev. 2000 Feb;10(1):17–25. doi: 10.1016/s0959-437x(99)00050-7. [DOI] [PubMed] [Google Scholar]
  24. Lustig A. J. Mechanisms of silencing in Saccharomyces cerevisiae. Curr Opin Genet Dev. 1998 Apr;8(2):233–239. doi: 10.1016/s0959-437x(98)80146-9. [DOI] [PubMed] [Google Scholar]
  25. Lustig A. J., Petes T. D. Identification of yeast mutants with altered telomere structure. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1398–1402. doi: 10.1073/pnas.83.5.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Matsuura A., Naito T., Ishikawa F. Genetic control of telomere integrity in Schizosaccharomyces pombe: rad3(+) and tel1(+) are parts of two regulatory networks independent of the downstream protein kinases chk1(+) and cds1(+). Genetics. 1999 Aug;152(4):1501–1512. doi: 10.1093/genetics/152.4.1501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Meluh P. B., Koshland D. Budding yeast centromere composition and assembly as revealed by in vivo cross-linking. Genes Dev. 1997 Dec 15;11(24):3401–3412. doi: 10.1101/gad.11.24.3401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mills K. D., Sinclair D. A., Guarente L. MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks. Cell. 1999 May 28;97(5):609–620. doi: 10.1016/s0092-8674(00)80772-2. [DOI] [PubMed] [Google Scholar]
  29. Moretti P., Freeman K., Coodly L., Shore D. Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1. Genes Dev. 1994 Oct 1;8(19):2257–2269. doi: 10.1101/gad.8.19.2257. [DOI] [PubMed] [Google Scholar]
  30. Naito T., Matsuura A., Ishikawa F. Circular chromosome formation in a fission yeast mutant defective in two ATM homologues. Nat Genet. 1998 Oct;20(2):203–206. doi: 10.1038/2517. [DOI] [PubMed] [Google Scholar]
  31. Nislow C., Ray E., Pillus L. SET1, a yeast member of the trithorax family, functions in transcriptional silencing and diverse cellular processes. Mol Biol Cell. 1997 Dec;8(12):2421–2436. doi: 10.1091/mbc.8.12.2421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Paciotti V., Clerici M., Lucchini G., Longhese M. P. The checkpoint protein Ddc2, functionally related to S. pombe Rad26, interacts with Mec1 and is regulated by Mec1-dependent phosphorylation in budding yeast. Genes Dev. 2000 Aug 15;14(16):2046–2059. [PMC free article] [PubMed] [Google Scholar]
  33. Porter S. E., Greenwell P. W., Ritchie K. B., Petes T. D. The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res. 1996 Feb 15;24(4):582–585. doi: 10.1093/nar/24.4.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Renauld H., Aparicio O. M., Zierath P. D., Billington B. L., Chhablani S. K., Gottschling D. E. Silent domains are assembled continuously from the telomere and are defined by promoter distance and strength, and by SIR3 dosage. Genes Dev. 1993 Jul;7(7A):1133–1145. doi: 10.1101/gad.7.7a.1133. [DOI] [PubMed] [Google Scholar]
  35. Ritchie K. B., Mallory J. C., Petes T. D. Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1999 Sep;19(9):6065–6075. doi: 10.1128/mcb.19.9.6065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Skehel P. A., Martin K. C., Kandel E. R., Bartsch D. A VAMP-binding protein from Aplysia required for neurotransmitter release. Science. 1995 Sep 15;269(5230):1580–1583. doi: 10.1126/science.7667638. [DOI] [PubMed] [Google Scholar]
  37. Stone E. M., Pillus L. Activation of an MAP kinase cascade leads to Sir3p hyperphosphorylation and strengthens transcriptional silencing. J Cell Biol. 1996 Nov;135(3):571–583. doi: 10.1083/jcb.135.3.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Strahl-Bolsinger S., Hecht A., Luo K., Grunstein M. SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev. 1997 Jan 1;11(1):83–93. doi: 10.1101/gad.11.1.83. [DOI] [PubMed] [Google Scholar]
  39. Thomas B. J., Rothstein R. Elevated recombination rates in transcriptionally active DNA. Cell. 1989 Feb 24;56(4):619–630. doi: 10.1016/0092-8674(89)90584-9. [DOI] [PubMed] [Google Scholar]
  40. Velculescu V. E., Zhang L., Zhou W., Vogelstein J., Basrai M. A., Bassett D. E., Jr, Hieter P., Vogelstein B., Kinzler K. W. Characterization of the yeast transcriptome. Cell. 1997 Jan 24;88(2):243–251. doi: 10.1016/s0092-8674(00)81845-0. [DOI] [PubMed] [Google Scholar]
  41. Wach A., Brachat A., Pöhlmann R., Philippsen P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994 Dec;10(13):1793–1808. doi: 10.1002/yea.320101310. [DOI] [PubMed] [Google Scholar]
  42. Weinert T. A., Kiser G. L., Hartwell L. H. Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev. 1994 Mar 15;8(6):652–665. doi: 10.1101/gad.8.6.652. [DOI] [PubMed] [Google Scholar]
  43. Zhou Z., Elledge S. J. DUN1 encodes a protein kinase that controls the DNA damage response in yeast. Cell. 1993 Dec 17;75(6):1119–1127. doi: 10.1016/0092-8674(93)90321-g. [DOI] [PubMed] [Google Scholar]

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