The impact of a negligent G2/M checkpoint on genomic instability and cancer induction

Abstract

How do DNA damage response pathways respond to low levels of DNA damage? Understanding this is essential when assessing environmental cancer risk. This Perspective considers the impact of a negligent G2/M checkpoint on genomic stability and cancer risk. 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.