Fig. 1: A kinetic model of DNA replication.

a Replication initiates at specific origins that are licensed by the end of G1 phase. During S phase, replication forks progress bidirectionally from origins, passively replicating DNA until they merge with forks from adjacent origins or reach chromosome ends to complete replication and enter G2. In this example, three origins (ORIs 1, 2, and 3) fire at different times, with nascent DNA strands shown in red. At the end of replication, two identical copies of the original template are formed. b Illustration of the expected inverse but non-trivial correlation between firing rates (top) and replication timing (bottom, with an inverted y-axis). In a model where the firing time of each origin is an exponentially distributed random variable, the firing rate is the parameter of this distribution and tends to decrease as replication timing increases, indicating that regions with higher firing rates replicate earlier in S phase. Replication timing, measured by Repli-seq, shows the average replication time across a cell population, with peaks corresponding to potential origins. ORI 2 is in a late-replicating region, while ORI 3 replicates earlier, as indicated by their relative positions on the timing curve. Adapted from Hulke et al.⁷⁰.