The proteasome factor Bag101 binds to Rad22 and suppresses homologous

AlthoughRAD52playsacriticalroleintheinitiationofhomologousrecombination(HR)byfacilitatingthereplacement of RPA with RAD51, the mechanism controlling RAD52 remains elusive. Here, we show thatBag101,afactorimplicatedinproteasomefunctioning,regulatesRAD52proteinlevelsandsubsequentHR.LC-MS/MS analysis identified Bag101 which binds to Rad22, the fission yeast homologue of RAD52.Bag101 reduced HR frequency through its overexpression and conversely, HR frequencies were enhancedwhen it was deleted. Consistent with this observation, Rad22 protein levels was reduced in cells wherebag101 was overexpressed even when Rad22 transcription was up-regulated, suggesting the operation ofproteasome-mediated Rad22 degradation. Indeed, Rad22 protein levels were stabilized in proteasomemutants.Rad22physicallyinteractedwiththeBAGdomainofBag101,andalackofthisdomainenhancedHR frequency. Similarly, radiation exposure triggered the dissociation of these proteins so that Rad22 wasstabilized and able to enhance HR.