FIG. 1.

Direct and indirect sources of DSBs. (A) A DSB can be formed directly by, for example, ionizing radiation. This results in the production of two free DNA ends. (B) If a replication fork encounters a nick in the template strand, an arm will detach to generate a single DSB. This is commonly referred to as replication fork collapse. (C) Following replication fork stalling due to replisome defects, or because there is damage or a block in the template strands, several fates are possible (see references 127, 202, and 205). Replication may restart de novo downstream of the damage without repair. Alternatively, the replication fork may undergo reversal to form a Holliday junction. In this case, the free end of the Holliday junction can be degraded by RecBCD to reform a fork and allow replisome reassembly. Replication can also continue after DNA repair by resorbing the Holliday junction to reform a fork. Otherwise, the Holliday junction may be cleaved to produce a single-ended DSB as in B. All of these DSBs are substrates for RecBCD-dependent recombinational repair.