Two S-phase checkpoint responses in S. cerevisiae. The S-phase checkpoint is triggered in the DNA damage signaling pathway by replication protein A (RPA)-coated DNA (red circles) resulting from ssDNA repair intermediates, resected ends of double-stranded breaks, or collapsed replication forks. In the replication stress signaling pathway, the S-phase checkpoint is triggered by stalled replication forks (α, δ, ε; replicative DNA polymerases). The two signaling pathways converge at Mec1/Ddc2, which phosphorylates Rad53 with the help of Rad9 (DNA damage) or Mrc1 (replication stress). Phospho-Rad53 then activates Dun1, which, in turn, inactivates three repressors (Sml1, Crt1, and Dif1) of RNR. RNR generates dNDPs from NDPs, which are then converted to dNTPs by nucleoside diphosphate kinases. Higher dNTP concentrations facilitate DNA repair and replication fork restart. Blue lines are signals that increase dNTP pools. Red lines are signals that repress dNTP pools. Adapted from ref. 63.