Figure 2.

HR at one-ended DSBs. One-ended DSBs are repaired by HR processes, likely using a second break end generated from an approaching replication fork. HR is initiated by Rad51-mediated base pairing of the resected break end to a homologous sequence. For DNA repair synthesis and HR to proceed, Rad51 needs to be removed by Rad54, a step which is postponed until G2 phase due to the G2-specific activation of Rad54 by Nek1. This ensures that DNA repair synthesis starts at a time when the second break end is available. The dHJ subpathway of HR involves second-end capture before processing the joint molecules, providing an intrinsic feature to control for the availability of a second break end. SDSA, in contrast, involves the displacement of the synthesized strand from the homologous donor, a step which could occur before the second end is created and bears the risk to join break ends from different DSBs. Joining incorrect break ends can also occur if one-ended DSBs are repaired by alt-NHEJ or by BIR processes that are aborted before a second break end is available. The choice between the dHJ pathway and SDSA is regulated by the chromatin remodeler ATRX.