Fig. 2.

SNF2-family translocases and RAD51 mediate fork reversal. The translocases SMARCAL1, ZRANB3 and HLTF may act in a sequential manner. A: SMARCAL1, recruited and stimulated by RPA, may catalyse initial fork reversal. Once RPA has been evicted, ZRANB3 activity will no longer be suppressed, allowing further fork reversal. B: HLTF polyubiquitinates PCNA, which can recruit ZRANB3 to forks – suggesting ZRANB3 may act downstream of HLTF. C: Differential levels of RAD51 are required for fork reversal versus fork protection. Strong, near complete, RAD51 depletion prevents fork reversal, leading to fork protection. Weaker depletion leaves sufficient RAD51 capable of promoting fork reversal but not enough to support fork protection, leading to degradation by MRE11 and other nucleases.