Roles and risks of DSB repair factories in mammalian cells. DSBs occurring in the G2 phase of the cell cycle and repaired by HDR cluster into repair domains or factories (shown in pink) to facilitate repair reactions, such as DNA end-processing, the initial step of HDR. DSBs occurring in G1 that cannot be routinely repaired by NHEJ, such as DSBs generated within highly transcribed genes, are thought to cluster into domains (shown in blue) for temporary shielding from repair until G2, when HDR can be initiated. Bringing DSBs in close proximity within spatially distinct domains (shown in yellow) could also favor abnormal chromosome rearrangements, such as translocations.