Pkc1 and Slt2 connections with the DNA damage response. This scheme represents the possible roles of Pkc1 and Slt2 related to the response to genotoxic stress. Pkc1 participates in the optimal activation of the DNA integrity checkpoint upstream or downstream of the Mec1/Tel1 apical kinases. Mec1/Tel1, in turn, mediate phosphorylation of Pkc1 by Hrr25 kinase after DNA damage. This regulation is involved in the expression of the RNR3 gene. Pkc1 is also linked to nucleotide biosynthesis, by regulating the CTP synthetase. Slt2 is activated by genotoxic stress through the inactivation of phosphatase Msg5. Possible Slt2 effectors include: Swe1, which is important for bud morphogenesis and G2/M arrest, whose DNA-damage induced degradation depends on Slt2; Cyclin C, an inducer of programmed cell death responsible for the hypersensitivity of slt2 mutants to genotoxic treatments; Whi7, a Start repressor regulated by Slt2 whose overexpression suppresses the checkpoint mutation; and Mrc1, a DNA integrity checkpoint adaptor protein that is regulated by Slt2 to stop DNA replication under certain conditions. Although the details of most of these connections are unknown, a scenario is beginning to emerge in which Pkc1 and Slt2 are important players in the response to genotoxic stress.