Fig. 8. Ccr4 and Dun1 collaborate to inhibit Crt1 activity and to promote induction of the DNA-damage gene regulon after replication stress. Ccr4 regulates CRT1 mRNA poly(A) tail length, which may influence translation and thereby levels of Crt1 protein. The Mec1-Rad53-Dun1 checkpoint kinase cascade phosphorylates and inhibits Crt1 repressor activity at DNA-damage-inducible promoters. Loss of either regulatory branch results in HU sensitivity; simultaneous loss of both regulatory branches causes severe and irreversible HU lethality.