Checkpoint adaptation in human cells

Checkpoint adaptation was originally described in Saccharomyces cerevisiae as the ability to divide following a sustained checkpoint arrest in the presence of unrepairable DNA breaks. A process of checkpoint adaptation was also reported in Xenopus in response to the replication inhibitor aphidicolin. Recently, we showed that checkpoint adaptation also occurs in human cells. Although cells undergoing checkpoint adaptation will frequently die in subsequent cell cycles owing to excessive DNA damage, some of the cells may be able to survive and proliferate with damaged DNA. Thus, checkpoint adaptation in human cells may potentially promote genomic instability and lead to cancer. Here, I discuss the current evidence for checkpoint adaptation in human cells and possible mechanisms and implications of this phenomenon.