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Gene Review

ARG1  -  argininosuccinate synthase

Saccharomyces cerevisiae S288c

Synonyms: Argininosuccinate synthase, Citrulline--aspartate ligase, O1228, YOL058W
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High impact information on ARG1

  • By recruiting an arginine-regulated repressor, Gcn4p can precisely modulate its activation function at ARG1 according to the availability of arginine [1].
  • Importantly, Spt4p is required for Paf1C occupancy at ARG1 (and other genes) and for Paf1C association with Ser5-phosphorylated Pol II in cell extracts, whereas Spt4p-Pol II association is independent of Paf1C [2].
  • Additionally, we found that increasing the ubiquitylation state of H2B inhibited the expression of the ARG1 gene, whose repression was previously shown to require the RAD6 ubiquitin ligase [3].
  • Recruitment of Mediator, by contrast, occurs independently of the other coactivators at ARG1 [4].
  • Recruitment of all three coactivators to ARG1 is independent of the TATA element and preinitiation complex formation, whereas efficient recruitment of the general transcription factors requires the TATA box [5].

Biological context of ARG1

  • The impairment of Gcn4p binding in cyc8Delta and tup1Delta cells is severe enough to reduce recruitment of SAGA, Srb mediator, TATA binding protein, and RNA polymerase II to the ARG1 and ARG4 promoters, accounting for impaired transcriptional activation of these genes in both mutants [6].
  • Since overexpression of FPR4 does not suppress the reduced expression of the ARG1 promoter found in tom1 deletion strains, Tom1p probably has one or more functions beyond its involvement in gene expression [7].
  • In this work, we have analyzed the time course of the incorporation of radioactive precursors into ARG1 and ARG3 mRNAs and the kinetics of their decay under different regulatory statuses [8].
  • We have found that the coordinated regulation of ARG1 requires components of the SAGA chromatin-remodeling complex [9].
  • Up-regulation of ARG1 in the absence of Gcn5p also correlated with increased binding of TATA-binding protein to the promoter [9].

Associations of ARG1 with chemical compounds

  • Transcription of the arginine biosynthetic gene ARG1 is repressed by the ArgR/Mcm1p complex in arginine-replete cells and activated by Gcn4p, a transcription factor induced by starvation for any amino acid [1].
  • We show that all four subunits of the arginine repressor are recruited to ARG1 by Gcn4p in cells replete with arginine but starved for isoleucine/valine [1].
  • The Saccharomyces cerevisiae ARG1 gene coding for argininosuccinate synthetase has been isolated and the nucleotide sequence of both its control region and of its amino terminal end coding region determined [10].
  • The tRNA Arg1, tRBA Lys2 and tRNA Leu, which belong to two-codon families ending in a purine, have a modified uridine in the wobble position, which prevents misreading of C and U [11].

Physical interactions of ARG1

  • We show that Paf1C is not recruited directly by the activator Gcn4p but is dependent on preinitiation complex assembly and Ser5 carboxy-terminal domain phosphorylation for optimal association with ARG1 coding sequences [2].

Regulatory relationships of ARG1

  • In addition, analysis of an ada2 rad6 deletion strain indicated that the SAGA acetyltransferase complex and Rad6 act in the same pathway to repress ARG1 in rich medium [12].

Other interactions of ARG1


Analytical, diagnostic and therapeutic context of ARG1

  • Chromatin immunoprecipitations using antibodies to acetylated H3 confirmed that a decrease in the level of acetylated histones at the ARG1 promoter correlated with increased ARG1 expression [9].


  1. Recruitment of the ArgR/Mcm1p repressor is stimulated by the activator Gcn4p: a self-checking activation mechanism. Yoon, S., Govind, C.K., Qiu, H., Kim, S.J., Dong, J., Hinnebusch, A.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. The Spt4p subunit of yeast DSIF stimulates association of the Paf1 complex with elongating RNA polymerase II. Qiu, H., Hu, C., Wong, C.M., Hinnebusch, A.G. Mol. Cell. Biol. (2006) [Pubmed]
  3. The deubiquitylation activity of Ubp8 is dependent upon Sgf11 and its association with the SAGA complex. Lee, K.K., Florens, L., Swanson, S.K., Washburn, M.P., Workman, J.L. Mol. Cell. Biol. (2005) [Pubmed]
  4. Simultaneous recruitment of coactivators by Gcn4p stimulates multiple steps of transcription in vivo. Govind, C.K., Yoon, S., Qiu, H., Govind, S., Hinnebusch, A.G. Mol. Cell. Biol. (2005) [Pubmed]
  5. Interdependent recruitment of SAGA and Srb mediator by transcriptional activator Gcn4p. Qiu, H., Hu, C., Zhang, F., Hwang, G.J., Swanson, M.J., Boonchird, C., Hinnebusch, A.G. Mol. Cell. Biol. (2005) [Pubmed]
  6. Activator Gcn4p and Cyc8p/Tup1p are interdependent for promoter occupancy at ARG1 in vivo. Kim, S.J., Swanson, M.J., Qiu, H., Govind, C.K., Hinnebusch, A.G. Mol. Cell. Biol. (2005) [Pubmed]
  7. The yeast peptidyl proline isomerases FPR3 and FPR4, in high copy numbers, suppress defects resulting from the absence of the E3 ubiquitin ligase TOM1. Davey, M., Hannam, C., Wong, C., Brandl, C.J. Mol. Gen. Genet. (2000) [Pubmed]
  8. Arginine-specific repression in Saccharomyces cerevisiae: kinetic data on ARG1 and ARG3 mRNA transcription and stability support a transcriptional control mechanism. Crabeel, M., Lavalle, R., Glansdorff, N. Mol. Cell. Biol. (1990) [Pubmed]
  9. Components of the SAGA histone acetyltransferase complex are required for repressed transcription of ARG1 in rich medium. Ricci, A.R., Genereaux, J., Brandl, C.J. Mol. Cell. Biol. (2002) [Pubmed]
  10. Arginine repression of the Saccharomyces cerevisiae ARG1 gene. Comparison of the ARG1 and ARG3 control regions. Crabeel, M., Seneca, S., Devos, K., Glansdorff, N. Curr. Genet. (1988) [Pubmed]
  11. Codon reading patterns in Saccharomyces cerevisiae mitochondria based on sequences of mitochondrial tRNAs. Sibler, A.P., Dirheimer, G., Martin, R.P. FEBS Lett. (1986) [Pubmed]
  12. The E2 ubiquitin conjugase Rad6 is required for the ArgR/Mcm1 repression of ARG1 transcription. Turner, S.D., Ricci, A.R., Petropoulos, H., Genereaux, J., Skerjanc, I.S., Brandl, C.J. Mol. Cell. Biol. (2002) [Pubmed]
  13. IRA2, a second gene of Saccharomyces cerevisiae that encodes a protein with a domain homologous to mammalian ras GTPase-activating protein. Tanaka, K., Nakafuku, M., Tamanoi, F., Kaziro, Y., Matsumoto, K., Toh-e, A. Mol. Cell. Biol. (1990) [Pubmed]
  14. Genetic mapping of arg1 and arg8 in Saccharomyces cerevisiae by trisomic analysis combined with interallelic complementation. Hilger, F., Mortimer, R.K. J. Bacteriol. (1980) [Pubmed]
  15. Isolation and characterization of Saccharomyces cerevisiae mutants deficient in S-adenosylmethionine decarboxylase, spermidine, and spermine. Cohn, M.S., Tabor, C.W., Tabor, H. J. Bacteriol. (1978) [Pubmed]
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