Model for mitotic turnover of Ndd1.

<p>In the absence of DNA damage, Ndd1 is phosphorylated by Cdk1, which promotes Ndd1 transcriptional activity but also enables SCF^Grr1 to recognize Ndd1 as a substrate. Ndd1 is therefore ubiquitinated and subsequently degraded. In response to DNA damage, Swe1 levels are increased, and Cdk1 is inhibited by phosphorylation which lowers its activity several fold. Ndd1 is no longer recognized by Grr1 and is therefore stabilized. Mec1 and Tel1 are important for maintaining high levels of phospho-Cdk1, and therefore help to stabilize Ndd1, either by promoting Swe1 activity or by inhibiting the phosphatase Mih1 (homolog of Cdc25). While Ndd1 is stabilized, its activity is independently inhibited by Rad53-dependent phosphorylation, leading to the accumulation of inhibited Ndd1. We speculate that maintaining this inhibited pool of Ndd1 may allow the cell to rapidly re-enter the cell cycle once the damage is repaired and the checkpoint is turned off.