Patent ID: 6566056
Filing Date: 2003-05-20
Classification: A61K,C07K

Abstract:
A method of identifying compensatory mutations in TP53 which suppress dominant-negative TP53 mutant phenotypes comprising the steps of:providing a cell comprising: (i) a reporter gene which is selectable, wherein the reporter gene is operably linked to a DNA sequence to which human p53 specifically binds; and (ii) a first fusion gene which expresses a dominant-negative allele of human p53 in the cell, the fusion gene comprising a promoter operably linked to a human p53 coding sequence; introducing into the cell a population of DNA molecules comprising a second fusion gene, wherein the second fusion gene comprises a promoter operably linked to a mutagenized human p53 coding sequence; and selecting for phenotypic revertants of the dominant-negative allele of human TP53 using the selectable phenotype of the reporter gene, wherein a phenotypic revertant which contains said second fusion gene identifies said second fusion gene as comprising a compensatory mutation in TP53 which suppresses dominant-negative TP53 mutant phenotypes.