Processing of Damaged DNA Ends for Double-Strand Break Repair in Mammalian Cells

Figure 5

Resolution of damaged termini for HRR. In HRR, following its initiation by MRN/CtIP, 5′→3′ exonucleolytic resection generates 3′-overhangs, one of which invades a sister duplex of the same sequence. Extension of this 3′-end (dashed line) enlarges the D-loop until it can be captured by the other 3′-overhang. Extension of this overhang followed by resolution of crossover structures restores an intact DNA duplex. Blocked 5′-termini must be removed before 5′→3′ exonucleolytic resection, probably by CtIP-dependent endonuclease activity. Removal of blocked 3′-termini could occur either before or after strand exchange but must occur before the respective extension steps.