(A) Progression through the four stages of the eukaryotic cell cycle depends on the activity of cyclin-dependent kinases (CDKs): when CDK1 is phosphorylated by Wee1 it becomes inactive and stops the cell cycle from progressing. De-phosphorylation by the Cdc25 phosphatase re-activates CDK1, allowing the cell cycle to continue to the next stage. (B) During infection, U. maydis arrests its cell cycle at the G2 stage using two distinct mechanisms. In the first mechanism (left) pheromones released from mating cells prior to fusion activate the Kpp2 signaling cascade, causing the Crk1-Pcl12 complex to phosphorylate the importin protein Kap123 so it can no longer import Cdc25 into the nucleus. Activation of Kpp2 also triggers down-regulation of the hls1 gene, which encodes a kinase that normally represses Wee1. This leads to increased Wee1 activity and inhibition of CDK1. Once the mating cells have fused, a second mechanism regulated by a homeodomain transcriptional regulator called b-factor (right) keeps the cell cycle arrested at G2 by: i) activating the DNA damage response (DDR) which causes Cdc25 to become phosphorylated and bind to a protein called Bmh1: this interaction ensures that Cdc25 is retained in the cytoplasm and cannot activate CDK1; ii) triggering the transcription of the biz1 gene, which in turn represses the transcription of the protein Clb1, which is needed to activate CDK1; iii) repressing the transcription of hsl1 gene that leads to an increase in phosphorylated inactive CDK1.