fig2

Figure 2. DSB repair by NHEJ and HR. Pathway choice is determined by end-resection, prevented by 53BP1, or promoted by BRCA1/MRN and Exo1/Dna2 exonucleases. (Left) NHEJ of unresected DSB ends initiates with Ku70/80 binding to ends and recruitment of DNA-PKcs to form the activated DNA-PK holoenzyme. Artemis is required to trim certain types of end-structures, and small gaps may be filled with polymerases m and l prior to LigIV/XRCC4/XLF-mediated ligation. NHEJ repair usually produces small indels (1-20-bp deletions, few-bp insertions). (Right) Resected 3’ single-strand ends are coated with RPA, which is then exchanged with RAD51, mediated by BRCA2, RAD52, RAD54, and RAD51 paralogs. The RAD51 nucleoprotein filament seeks and invades a homologous donor duplex (grey). RAD51 dissociates before repair synthesis; the newly synthesized strand (red dash) is released from the donor duplex and anneals with the complementary strand on the opposite side of the DSB. A second round of repair synthesis and nick sealing completes repair. DDR: DNA damage response; DSB: DNA double-strand break; NHEJ: non-homologous end-joining; HR: homologous recombination