Figure 7. Model depicting differential control of genome stability in ESCs and proliferating somatic cells.

Under-replicated regions and residual DNA damage are unavoidably present at the end of each S-phase in both ESCs and somatic cells. However, owing to the brief gap phases, ESCs channel a high number of these lesions in the following S-phase and protect genome integrity by extensive fork reversal and replication-coupled repair. Conversely, differentiated cells have prolonged gap phases, assemble 53BP1 NBs and repair most of these lesions before S-phase entry (see also Supplementary Fig. 7d).