Phosphorylation: The Molecular Switch of Double-Strand Break Repair

Figure 2

Phosphorylation events in the initiation of HR. After DNA damage is inflicted, the MRN complex processes the ends of the DSBs. BRCA1 is phosphorylated by ATM and CHK2 and regulates the MRN complex. RPA then associates with the 3′ ssDNA overhangs and becomes phosphorylated. Rad52 binds RPA and displaces it to allow for Rad51 binding. BRCA2 binds to Rad51 until BRCA2 becomes phosphorylated, releasing Rad51 and allowing it to localize to the DSB with Rad52. HR-mediated repair continues: Rad51 then forms a nucleoprotein filament that invades a homologous sequence and activates strand exchange to generate a crossover between the juxtaposed DNA.