Carbon Distribution Analysis on Mutations Responsible for Li-Fraumeni Syndrome

Abstract

Li-Fraumeni syndrome is an autosomal dominant hereditary disorder linked to germ line mutations of the p53 tumor suppressor protein. Native type p53 protein is a tumor suppressor protein that regulates the expression of a wide variety of genes involved in apoptosis, growth arrest, and inhibition of cell cycle progression, differentiation and accelerated DNA repair, senescence in response to genotoxic or cellular stress. Carbon analysis (CARBANA) tool available online was used to study the carbon content distribution profiles in p53 native-type and mutated proteins. Twelve p53 point mutations (M133T, A138P, P151S, P152L, Y163C, R175H, H193R, Y220C, R248Q, R273C, R273H and K292I) from Li-Fraumeni syndrome cases were investigated in this study. Results show that, 67% of mutants investigated at the mutation sites of the sequence, their carbon content distribution are normal and correspond to 0.3145 and the remaining 33% deviated from the normal carbon distribution. For the full sequence carbon analysis, the results showed no significant difference in carbon distribution among p53 mutants and native-type proteins. In point mutations, the size, number of carbon atoms, hydrophobic or hydrophilic nature of the newly substituted amino acids plays a key role in p53 carbon content distribution at the mutational sites. It was noted that, all p53 mutants were associated with health problems despite of some having normal carbon distribution in the mutation sites, therefore overall carbon distribution does not play a role in Li-Fraumeni Syndrome.