Fig. 1: HR-mediated DSB repair.

First, the MRN complex (MRE11/RAD50/NBS1), in cooperation with the ataxia-telangiectasia mutated (ATM) kinase and the chromatin remodelling machinery, recognises DSBs and induces signalling pathways. The subsequent steps of HR can be summarised as follows: (1) The resection of the DSB generates a 3’ ssDNA stretch, which is coated with the replication protein RPA; (2) and (3) the mediators (BRCA1, BRCA2, PALB2) replace RPA by RAD51 on the ssDNA, forming the RAD51-ssDNA filament, which then promotes the search for homology and the invasion of a duplex DNA molecule harbouring homologous sequences; this corresponds to the central pivotal step of HR; (4) capture of the second DSB; (5) DNA synthesis is then primed using the invading 3’ ssDNA; and (6) the resolution of the HR intermediates leads to gene conversions associated or not with crossover or synthesis-dependent strand annealing (SDSA) or break-induced replication (BIR) [4, 96, 97]. Some of the main factors that are mutated in hereditary breast or ovary cancer are shown in the figure.