Rad52 Conditional Knockout mouse models

Rad52, ortholog of human RAD52, encodes a single-stranded DNA annealing protein that assembles into undecameric rings, binds RPA-coated single-stranded DNA and catalyzes complementary strand annealing, driving single-strand annealing repair and break-induced replication as well as second-end capture during homologous recombination. Unlike its budding yeast counterpart it is not the principal RAD51 mediator in mammals, a role BRCA2 fulfills, and this is precisely why the mouse null is viable and nearly phenotypically silent with only modest recombination defects. That redundancy is the central design consideration: informative models place conditional or constitutive Rad52 loss on Brca1, Brca2 or Palb2 deficient backgrounds, where RAD52 becomes a synthetic lethal dependency and a validated small molecule target. Structure-guided knockins that disrupt the annealing groove or the RPA interaction while preserving ring assembly separate mechanism from protein abundance. Select by endpoint: compound conditional genetics for synthetic lethality, point knockins for target validation.

Conditional deletion of Rad52 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Rad52 floxed stock yields usable cohorts.