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Gene Review

ARG4  -  argininosuccinate lyase ARG4

Saccharomyces cerevisiae S288c

Synonyms: ASAL, Argininosuccinate lyase, Arginosuccinase, YHR018C
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Disease relevance of ARG4

  • However, a meiosis-specific increase in MNase hypersensitivity was no longer detected at the inactive insert-borne arg4 DSB site [1].
  • The ASL of M. maripaludis shares a high amino acid identity with ASLs from both bacterial and eukaryal origins and was able to complement both an argH Escherichia coli mutant and an arg4 yeast mutant, showing its extraordinary evolutionary conservation [2].

High impact information on ARG4

  • The single-stranded tails very in length, generating a gradient of single-strandedness that parallels the gradient of gene conversion frequencies in ARG4 [3].
  • Plasmids that replicate autonomously in Chlamydomonas reinhardii were constructed by inserting random DNA fragments from this alga into a plasmid containing the yeast ARG4 locus [4].
  • In the accompanying paper we describe the localization of an initiation site for gene conversion to the promoter region of the ARG4 gene of the yeast Saccharomyces cerevisiae [5].
  • When the microsatellite sequence was present at the ARG4 locus on homologous chromosomes, diploid cells undergoing meiosis generated an excess of tetrads containing a conversion of the region restricted to the region of the microsatellite close to the recombination-initiation double-strand break [6].
  • The combined data strongly suggest that numerous recombination events are restricted to the initiation side of the microsatellite as though progression of the strand exchange initiated at the ARG4 promoter locus was impaired by the repetitive sequence [6].

Biological context of ARG4

  • Combined with the observation that Pms1+ ARG4/arg4-nsp diploids produce 3 times more 3+:5m (wildtype:mutant) tetrads (+, +, +/m, m) than 5+:3m tetrads (+, +/m, m, m), these results indicate that, during meiosis, formation of heteroduplex DNA at ARG4 involves preferential transfer of the sense (nontranscribed) strand of the DNA duplex [7].
  • Of the two possible arg4-nsp/ARG4 mismatches (G.G and C.C), only C.C was detected in spores from mismatch repair-competent (Pms1+) diploids [7].
  • By using specifically marked HIS4 and ARG4 alleles, we showed that msh2 mutants displayed a severe defect in the repair of all base pair mismatches as well as 1-, 2- and 4-bp insertion/deletion mispairs [8].
  • It contains besides the ARG4 gene, another complete open reading frame (ORF) (YSD83) and a third incomplete one (DED81) [9].
  • The study of hyper- and hypo-recombinogenic constructs at the ARG4 locus, also revealed that the MNase sensitivity at the DSB site correlates with both the extent of DSBs and the rate of gene conversion [10].

Associations of ARG4 with chemical compounds

  • Similarly, the behavior of fusions of the leader sequence of CPA1 with those of ARG4 or GAL10 confirmed that the regions of this leader located upstream and downstream from the uORF are dispensable for the regulation by arginine [11].
  • Replacing Arg4 and Arg5 by alanine residues and shifting the Arg5 and Leu6 (in order to disturb amphiphilicity) resulted in reduction of the presequence import efficiency [12].

Other interactions of ARG4

  • A 51-bp region of telomeric DNA inserted upstream of either HIS4 or ARG4 very strongly stimulates recombination [13].
  • The predicted products of the genes share significant sequence similarity to their Saccharomyces cerevisiae counterparts, namely argininosuccinate lyase, PR-aminoimidazolesuccinocarboxamide synthase, and orotidine-5'-phosphate decarboxylase, respectively [14].
  • We describe the isolation and characterization of three new biosynthetic genes-ARG4, ADE1, and URA3-from the methylotrophic yeast Pichia pastoris [14].
  • None of these proteins is recruited to the Gcn4p target genes ARG4 and SNZ1, which are not regulated by ArgR/Mcm1p [15].
  • To uncover the regulatory mechanisms active in DSB formation, we have monitored the change in local chromatin structure at the ARG4 and CYS3 recombination hot spots over the course of meiosis [10].

Analytical, diagnostic and therapeutic context of ARG4


  1. Competitive inactivation of a double-strand DNA break site involves parallel suppression of meiosis-induced changes in chromatin configuration. Ohta, K., Wu, T.C., Lichten, M., Shibata, T. Nucleic Acids Res. (1999) [Pubmed]
  2. Functional conservation between the argininosuccinate lyase of the archaeon Methanococcus maripaludis and the corresponding bacterial and eukaryal genes. Cohen-Kupiec, R., Kupiec, M., Sandbeck, K., Leigh, J.A. FEMS Microbiol. Lett. (1999) [Pubmed]
  3. Extensive 3'-overhanging, single-stranded DNA associated with the meiosis-specific double-strand breaks at the ARG4 recombination initiation site. Sun, H., Treco, D., Szostak, J.W. Cell (1991) [Pubmed]
  4. Construction and characterization of autonomously replicating plasmids in the green unicellular alga Chlamydomonas reinhardii. Rochaix, J.D., van Dillewijn, J., Rahire, M. Cell (1984) [Pubmed]
  5. Double-strand breaks at an initiation site for meiotic gene conversion. Sun, H., Treco, D., Schultes, N.P., Szostak, J.W. Nature (1989) [Pubmed]
  6. (CA/GT)(n) microsatellites affect homologous recombination during yeast meiosis. Gendrel, C.G., Boulet, A., Dutreix, M. Genes Dev. (2000) [Pubmed]
  7. Detection of heteroduplex DNA molecules among the products of Saccharomyces cerevisiae meiosis. Lichten, M., Goyon, C., Schultes, N.P., Treco, D., Szostak, J.W., Haber, J.E., Nicolas, A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  8. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Alani, E., Reenan, R.A., Kolodner, R.D. Genetics (1994) [Pubmed]
  9. Sequence comparison of the ARG4 chromosomal regions from the two related yeasts, Saccharomyces cerevisiae and Saccharomyces douglasii. Adjiri, A., Chanet, R., Mezard, C., Fabre, F. Yeast (1994) [Pubmed]
  10. Changes in chromatin structure at recombination initiation sites during yeast meiosis. Ohta, K., Shibata, T., Nicolas, A. EMBO J. (1994) [Pubmed]
  11. A segment of mRNA encoding the leader peptide of the CPA1 gene confers repression by arginine on a heterologous yeast gene transcript. Delbecq, P., Werner, M., Feller, A., Filipkowski, R.K., Messenguy, F., Piérard, A. Mol. Cell. Biol. (1994) [Pubmed]
  12. Hydrophobic residues within the predicted N-terminal amphiphilic alpha-helix of a plant mitochondrial targeting presequence play a major role in in vivo import. Duby, G., Oufattole, M., Boutry, M. Plant J. (2001) [Pubmed]
  13. Transcription factors are required for the meiotic recombination hotspot at the HIS4 locus in Saccharomyces cerevisiae. White, M.A., Dominska, M., Petes, T.D. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  14. New selectable marker/auxotrophic host strain combinations for molecular genetic manipulation of Pichia pastoris. Lin Cereghino, G.P., Lin Cereghino, J., Sunga, A.J., Johnson, M.A., Lim, M., Gleeson, M.A., Cregg, J.M. Gene (2001) [Pubmed]
  15. 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]
  16. Mitotic recombination and localized DNA double-strand breaks are induced after 8-methoxypsoralen and UVA irradiation in Saccharomyces cerevisiae. Dardalhon, M., de Massy, B., Nicolas, A., Averbeck, D. Curr. Genet. (1998) [Pubmed]
  17. Sequence analysis of the ARG7 gene of Schizosaccharomyces pombe coding for argininosuccinate lyase. Expression of the gene in Saccharomyces cerevisiae. Loppes, R., Michels, R., Decroupette, I., Joris, B. Curr. Genet. (1991) [Pubmed]
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