Fig 1: Schematic representation of the DNA replication steps in the context of the cell cycle and of the ATR and SLFN11 replication checkpoints. DNA replication is initiated by recognition of replication origins scattered along the genome. A, In G1, active origins of replication are licensed by ORC, CDC6, CDT1, and MCM2-7, forming the pre-replication complex (pre-RC). B, At the G1-S transition, the pre-RC complex is fired by activation of kinases (DDK and CDK) and loading GINS and CDC45, thereby unwinding the DNA duplex and initiating the replication by DNA polymerases. C, Active replication forks are elongated by the replication machinery including helicases, PCNA and DNA polymerases throughout S-phase. D, The replication process is terminated when the bidirectional replication forks merge. The RepStress is monitored and modulated by replication checkpoints, ATR and SLFN11, which are both recruited to RPA filaments. While ATR produces a transient cell cycle arrest allowing DNA repair, SLFN11 produces an irreversible replication arrest.