Three different pathways prevent chromosome segregation in the presence of genotoxic stress.

<p>Molecular diagram showing the three pathways that block Mitotic Cyclin Dependent Kinase activity and anaphase in response to genotoxic stress. Swe1 and the S phase checkpoint effector kinase Rad53 are individually sufficient to block M-CDK activity. Our results place Swe1 as a downstream effector of the S phase checkpoint. M-CDK inhibition and Pds1/securin stabilization are individually sufficient to prevent anaphase. Only when the three pathways are disrupted cells fail to block the segregation of damaged or incompletely replicated chromosomes. In grey, regulatory pathways taken from previous works [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005468#pgen.1005468.ref023" target="_blank">23</a>–<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005468#pgen.1005468.ref028" target="_blank">28</a>]. The Spindle Assembly Checkpoint (SAC) is included in the model as it may also play a role in Pds1 stabilization [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005468#pgen.1005468.ref076" target="_blank">76</a>].