Figure 1.

Reduced Replication by Global and Local Mechanisms. The checkpoint could act to slow replication using either global or local mechanisms. Slowing replication in response to DNA damage involves regulation of origin firing and replication fork progression. Origin firing is a global checkpoint response in which origins are prevented from firing that are not directly affected by DNA damage. In contrast, checkpoint regulation of replication fork progression may be a local or a global response to DNA damage. If global, all replication forks, both those encountering DNA lesions and those unperturbed by damage would be slowed. If local, only forks directly encountering damaged template would be slowed in a checkpoint-dependent manner.