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dc.contributor.authorTrevisson, Eva-
dc.contributor.authorBurlina, Alberto-
dc.contributor.authorDoimo, Mara-
dc.contributor.authorPertegato, Vanessa-
dc.contributor.authorCasarin, Alberto-
dc.contributor.authorCesaro, Luca-
dc.contributor.authorNavas, Plácido-
dc.contributor.authorBasso, Giuseppe-
dc.contributor.authorSartori, Geppo-
dc.contributor.authorSalviati, Leonardo-
dc.date.accessioned2011-10-06T12:41:12Z-
dc.date.available2011-10-06T12:41:12Z-
dc.date.issued2009-08-24-
dc.identifier.citationThe Journal of Biological Chemistry 284(): 28926-28934 (2009)es_ES
dc.identifier.issn0021-9258-
dc.identifier.otherPMC2781438-
dc.identifier.otherPMID: 19703900-
dc.identifier.urihttp://hdl.handle.net/10261/40708-
dc.description9 páginas, 9 figuras, 2 tablas.es_ES
dc.description.abstractDeficiency of argininosuccinate lyase (ASL) causes argininosuccinic aciduria, an urea cycle defect that may present with a severe neonatal onset form or with a late onset phenotype. To date phenotype-genotype correlations are still not clear because biochemical assays of ASL activity correlate poorly with clinical severity in patients. We employed a yeast-based functional complementation assay to assess the pathogenicity of 12 missense ASL mutations, to establish genotype-phenotype correlations, and to screen for intragenic complementation. Rather than determining ASL enzyme activity directly, we have measured the growth rate in arginine-free medium of a yeast ASL(null) strain transformed with individual mutant ASL alleles. Individual haploid strains were also mated to obtain diploid, "compound heterozygous" yeast. We show that the late onset phenotypes arise in patients because they harbor individual alleles retaining high residual enzymatic activity or because of intragenic complementation among different mutated alleles. In these cases complementation occurs because in the hybrid tetrameric enzyme at least one active site without mutations can be formed or because the differently mutated alleles can stabilize each other, resulting in partial recovery of enzymatic activity. Functional complementation in yeast is simple and reproducible and allows the analysis of large numbers of mutant alleles. Moreover, it can be easily adapted for the analysis of mutations in other genes involved in urea cycle disorders.es_ES
dc.description.sponsorshipThis work was supported by Telethon Italy Grant GGP06256 and by Fondazione Città della Speranza.es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes_ES
dc.rightsclosedAccesses_ES
dc.subjectAlleleses_ES
dc.subjectArgininosuccinate lyasees_ES
dc.subjectGenetic vectorses_ES
dc.subjectGenotypees_ES
dc.subjectHaploidyes_ES
dc.subjectHeterozygotees_ES
dc.subjectPhenotypees_ES
dc.subjectSaccharomyces cerevisiaees_ES
dc.subjectUreaes_ES
dc.titleFunctional Complementation in Yeast Allows Molecular Characterization of Missense Argininosuccinate Lyase Mutationses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1074/jbc.M109.050195-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1074/jbc.M109.050195es_ES
dc.identifier.e-issn1083-351X-
dc.identifier.pmid19703900-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
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