Double-checking DNA synthesis

The replication and spindle assembly checkpoints work together to prevent premature mitosis, Magiera et al. report.

Cells need to copy their DNA before they can separate their chromosomes. The DNA replication checkpoint monitors the progress of the first step, and the spindle assembly checkpoint (SAC) regulates the second. Still uncertain is how cells dovetail the end of replication with the beginning of mitosis. If researchers disrupt DNA synthesis, the replication checkpoint kicks in and halts the cell cycle. Whether the checkpoint forestalls mitosis under normal circumstances remains unclear, however.

To find out, Magiera et al. turned yeast cells into procrastinators, deleting two cyclins to delay the beginning of S phase by 30 minutes. These cells are still copying their DNA when they should be entering mitosis, and the researchers found that this alteration postponed anaphase by 17 minutes.

Mec1, the yeast equivalent of ATR kinase, is a key protein for the replication checkpoint, and the team discovered that removing it from cells lacking the cyclins shortened the anaphase delay. Removing Mad2, a crucial component of the SAC, also allowed the cyclin-deficient yeast to begin mitosis slightly sooner. But deleting Mec1 and Mad2 caused cells to accumulate DNA damage, lose chromosomes, and die. The team’s findings indicate that the replication checkpoint and the SAC are active at low levels during S phase, protecting the cell’s genome by delaying mitosis until replication is complete.