ATR and TopBP1 oppose to control dormant origin activity and overall replication dynamics, providing a first defense against replication stress [OK-seq]

The first line of defense against this stress is the recruitment of extra-origins, called dormant, which assists constitutive origins in completing replication. To determine how the DNA replication checkpoint contributes to this compensation process in human cells, we set a dose-response assay that allows quantification of the compensation efficiencies, enabling accurate comparison of cells depleted of relevant proteins.

Results show that ATR activity is essential to dormant origin mobilization. In stark contradiction to what would be expected from its ATR-activating function, TopBP1 represses compensation and acts downstream of ATR. Therefore, our results instead design the TopBP1 function in replisome assembly as key to dormancy.