The tumor suppressor p53 has long been known to play a central role in maintaining a stable genome in the face of toxic insults through its role in promoting cell-cycle checkpoints, DNA repair, and apoptosis. However, p53 null cells still retain some function of certain checkpoint and repair processes, reducing the genomic changes that otherwise would occur if these mechanisms were absent. Accumulating evidence suggests that mutant forms of p53 proteins may drastically perturb these residual genome-stabilizing mechanisms through gain-of-function interactions with multiple proteins leading to a higher level of genomic instability than in p53 null cells. This review summarizes the current body of evidence that mutp53 plays a role in promoting various forms of genomic instability and provides an overview of current mechanistic proposals.
Copyright © 2011 Wiley Periodicals, Inc.