Fig. 7
From: Replication fork reversal triggers fork degradation in BRCA2-defective cells
Model for the role of different HR factors in stalled fork remodeling and protection. With the help of ZRANB3 and PARP activity, RAD51 promotes efficient reversal of stalled replication forks independently of BRCA2. Upon initial resection of reversed forks, RAD51 is efficiently loaded by BRCA2 on regressed arms to limit MRE11/PTIP/RAD52-dependent nucleolytic degradation and promote efficient fork restart. In BRCA2-defective cells, deregulated MRE11-dependent degradation of reversed forks leads to ssDNA accumulation and chromosomal breaks. Limiting reversed fork degradation restores fork integrity and prevents chromosomal breakage. Preventing fork reversal also restores fork integrity in BRCA2-defective cells—by reduced availability of degradation substrates—but leads to increased chromosomal breakage, and is thus detrimental for genome stability
