Marks to stop the clock: histone modifications and checkpoint regulation in the DNA damage response.

DNA damage from endogenous and exogenous sources occurs throughout the cell cycle. In response to this damage, cells have developed a series of biochemical responses that allow them to recover from DNA damage and prevent mutations from being passed on to daughter cells. An important part of the DNA damage response is the ability to halt the progression of the cell cycle, allowing damaged DNA to be repaired. The cell cycle can be halted at semi-discrete times, called checkpoints, which occur at critical stages during the cell cycle. Recent work in our laboratory and by others has shown the importance of post-translational histone modifications in the DNA damage response. While many histone modifications have been identified that appear to facilitate repair per se, there have been surprisingly few links between these modifications and DNA damage checkpoints. Here, we review how modifications to histone H2A serine 129 (HSA129) and histone H3 lysine 79 (H3K79) contribute to the stimulation of the G1/S checkpoint. We also discuss recent findings that conflict with the current model of the way methylated H3K79 interacts with the checkpoint adaptor protein Rad9.