Journal Article

Simple identification of dominant p53 mutants by a yeast functional assay.

A Inga, S Cresta, P Monti, A Aprile, G Scott, A Abbondandolo, R Iggo and G Fronza

in Carcinogenesis

Volume 18, issue 10, pages 2019-2021
Published in print October 1997 | ISSN: 0143-3334
Published online October 1997 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/18.10.2019
Simple identification of dominant p53 mutants by a yeast functional assay.

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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.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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