title: Simple identification of dominant p53 mutants by a yeast functional assay.
abstract: Analysis of families with germline p53 mutations shows that the mutant p53 allele behaves as a dominant oncogene at the genetic level, although it behaves as a recessive oncogene at the cellular level, since tumours invariably show mutation or loss of both wild-type alleles. At the biochemical level it is possible that some clinically important mutant p53 proteins may be carcinogenic through a dominant mechanism. We show that p53 mutants can be readily classified according to their dominant potential using a simple yeast functional assay. Wild-type p53 is constitutively expressed from a TRP1 vector, p53 mutants are expressed from an otherwise identical LEU2 vector and net transcriptional activity is scored using an ADE2-based reporter. Twenty seven p53 mutants were tested: 19 were recessive, i.e. gave white colonies, and eight showed dominant activity, i.e. gave pink/red colonies. This simple assay should facilitate studies on p53 dominance.
authors.affiliation: CSTA-Mutagenesis Laboratory, National Institute for Research on Cancer (IST), Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Inga
authors.forename: S
authors.initials: S
authors.lastname: Cresta
authors.forename: P
authors.initials: P
authors.lastname: Monti
authors.forename: A
authors.initials: A
authors.lastname: Aprile
authors.forename: G
authors.initials: G
authors.lastname: Scott
authors.forename: A
authors.initials: A
authors.lastname: Abbondandolo
authors.forename: R
authors.initials: R
authors.lastname: Iggo
authors.forename: G
authors.initials: G
authors.lastname: Fronza
mesh_terms: D018076:DNA, Complementary / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development
chemical_list: D018076:DNA, Complementary