The Impact of a Negligent G2/M Checkpoint on Genomic Instability and Cancer Induction

DNA damage responses (DDR) encompass DNA repair and signal transduction pathways that effect cell cycle checkpoint arrest and/or apoptosis. How DDR pathways respond to low levels of DNA damage, including low doses of ionizing radiation, is crucial for assessing environmental cancer risk. It has been assumed that damage-induced cell cycle checkpoints respond to a single double strand break (DSB) but the G2/M checkpoint, which prevents entry into mitosis, has recently been shown to have a defined threshold of 10-20 DSBs. Here, we consider the impact of a negligent G2/M checkpoint on genomic stability and cancer risk.