RAD52 prevents accumulation of -dependent replication gaps at perturbed replication forks in human cells.

Replication gaps can arise as a consequence of perturbed DNA replication and their accumulation might undermine the stability of the genome. Loss of RAD52, a protein involved in the regulation of fork reversal, promotes accumulation of parental ssDNA gaps during replication perturbation. Here, we demonstrate that this is due to the engagement of downstream of the extensive degradation of perturbed replication forks after their reversal, and is not dependent on PrimPol. is hyper-recruited at parental ssDNA in the absence of RAD52, and this recruitment is dependent on fork reversal enzymes and RAD51. Of note, we report that the interaction between and RAD51 is stimulated by RAD52 inhibition, and -dependent gap accumulation requires nucleation of RAD51 suggesting that it occurs downstream strand invasion. Altogether, our data indicate that RAD51- -dependent repriming is essential to promote fork restart and limit DNA damage accumulation when RAD52 function is disabled.