p53 mutation and mitotic infidelity

Chromosome instability (a high frequency of chromosomal loss and gain and g enome doubling, often referred to as karyotypic instability) is one of the major characteristics of cancer cells. It facilitates carcinogenesis by inc reasing the chance of specific mutations responsible for malignant phenotyp es. Chromosome instability in most cases reflects the occurrence of defecti ve mitosis, including unequal distribution of chromosomes to daughter cells and failure to undergo cytokinesis, which leads to generation of aneuploid cells. Both in vivo and in vitro, chromosome instabilibwwww has been shown to correlate with loss or mutation of the p53 armor suppressor protein the product of one of the most frequently mutated genes in cancer. The major f unction of p53 is to prevent cells from proceeding through the cell cycle w hen cells experience stress, insults, or errors that disturb the preprogram med cell cycle progression. During the last several years, significant adva nces have been made in understanding how p53 is involved in the regulation of mitosis and how loss or mutation of p53 affects mitotic fidelity, which will be the subject of this review.