Fig. 5.

Model of regulation of the length of D-loop extension by PCNA and choice of polymerase. HR can act on diverse substrates (e.g., DSBs formed by DNA-damaging agents or ssDNA gaps left behind replication fork). Irrespective of the inputs, HR proceeds by formation of D-loop, representing a common structure formed by an invading strand of the broken DNA into homologous template sequence, in order to copy the missing information. We propose that presence of PCNA on the D-loop might target the appropriate polymerase and determine the outcome of HR by regulating the extension length. When loaded, PCNA promotes a long extension track by Pol δ. In the absence of PCNA, on the other hand, Pol η may extend the D-loop generating shorter extension tracks, which could correlate with use in the gap repair and template switch events. The length of the extension might also be important for synthesis-dependent strand-annealing (SDSA) or double-strand break repair (DSBR), which are characterized, respectively, by displacement of the extended D-loop or stabilization of D-loop by second capture. PCNA loading may thus represent a regulatory point for appropriate choice of pathway. Alternatively, break-induced replication can take place when a second end of DSB is absent.