Regulation and functional analysis of the tumor suppressor gene product, p53

Abstract

The distribution and functional analysis of p53 codon 72 polymorphism have been investigated. The genotype frequency of p53Arg/p53Arg homozygotes was highest in the Chinese and Polish population, but lower in the Malays and Indians. Expressing alleles of p53 in healthy Chinese heterozygotes tend to express p53Pro allele whereas the Polish heterozygotes express either p53Arg or both (p53Pro/p53Arg). There seems to be a selection pressure on the expression of p53 alleles in different populations. These two p53 polymorphs showed different DNA repair capacity, p53Pro repaired better than p53Arg. Another interesting finding is, melanin production is more in presence of p53Pro than p53Arg form. This might be an indirect role of p53Pro to protect DNA from UV-induced damage. Investigation on p53 mutation along with polymorphism showed that polymorphism affects the drug sensitivity of these mutants. Thus, these two p53 polymorphs are different biologically and they have differential property in maintaining genomic integrity.