Cdk1 modulates the activity of several DNA damage checkpoint proteins. DNA damage and replication stress are sensed by a number of proteins that activate the PIKKs Mec1 and Tel1. These kinases activate a signal transduction pathway consisting of the adaptor proteins Mrc1 and Rad9 and the kinases Rad53, Dun1 and Chk1. Cdk1 may phosphorylate Rad9 to boost the signaling cascade. Cdk1 also phosphorylates Rad53, which may prevent checkpoint adaptation, but which may also affect processes involved in cell morphogenesis. Together, Mec1, Tel1, Rad53, Dun1 and Chk1 phosphorylate a number of effector proteins (only a subset of effectors is shown in this figure) that mediate the DNA damage response. Several of these effectors are also targeted by Cdk1, although the consequence of simultaneous phosphorylation by Rad53 and Cdk1 is unclear. Mec1/Tel1 and Cdk1 directly phosphorylate Sae2 to stimulate its nuclease activity, which is important for resection of DSBs, thereby channeling DSBs into the HR pathway. Full resection of DSBs also requires the activity of Dna2 and Sgs1. Phosphorylation of Dna2 by Cdk1 increases its nuclear import, while Cdk1 may affect Sgs1 by phosphorylating Srs2, which leads to formation of subcomplexes consisting of Srs2, Srs2-Mre11 and Sgs1-Mre11. Mec1/Tel1 and Cdk1 also directly phosphorylate Cdc13, resulting in recruitment of telomerase and telomere elongation. See text for details.