Model to show how cells respond to low levels of replicative stress. (a) Two adjacent clusters of origins (factories bounded by green circles) are shown on a single piece of DNA (black lines). Under normal circumstances (left), the upper factory is activated slightly earlier than the factory below, and each initiates three origins. Under low levels of replicative stress (right), replication forks are inhibited in the earlier replicating cluster, which promotes the firing of dormant origins as a direct consequence of stochastic origin firing. Replicative stress activates DNA damage checkpoint kinases, which preferentially inhibit the activation of the unfired later clusters/new factories. (b) A model showing two converging forks on a single piece of DNA (black lines) that have stalled (red bars). If a dormant origin is activated between them, replication can be rapidly rescued (left). If there is no dormant origin firing between the stalled forks (right), the DNA damage response can lead to recombination or induction of apoptosis.