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.