Single-strand breaks (SSBs) are recognized by a handful of proteins, including poly (ADP-ribose) polymerase (PARP) and RPA. PARP helps recruit DNA repair machinery to repair SSBs (blue shading). ATR is recruited to the site of damage and activates (phosphorylates) a variety of damage-sensing mediators, including CHK1, which in turn can activate p53 and, depending on other signals, pause the cell cycle until damage is repaired or induce apoptosis. Double-strand breaks (DSBs) recruit a variety of factors, including the M/R/N complex (MRE11, RAD50, and NBS1). This complex recruits and activates ATM, which phosphorylates DSB-sensing mediators, including CHK2. 53BP1 binds to M/R/N on loose DNA ends and promotes non-homologous end joining (NHEJ) repair (orange shading). During late S/G
2 phase, BRCA1 can be activated by ATM and compete with 53BP1 for binding at the M/R/N complex and aid resection of DNA ends to promote homologous recombination (HR) repair (green shading).