title: The proteasome factor Bag101 binds to Rad22 and suppresses homologous recombination.
abstract: Although RAD52 plays a critical role in the initiation of homologous recombination (HR) by facilitating the replacement of RPA with RAD51, the mechanism controlling RAD52 remains elusive. Here, we show that Bag101, a factor implicated in proteasome functioning, regulates RAD52 protein levels and subsequent HR. 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 enhanced when it was deleted. Consistent with this observation, Rad22 protein levels was reduced in cells where bag101 was overexpressed even when Rad22 transcription was up-regulated, suggesting the operation of proteasome-mediated Rad22 degradation. Indeed, Rad22 protein levels were stabilized in proteasome mutants. Rad22 physically interacted with the BAG domain of Bag101, and a lack of this domain enhanced HR frequency. Similarly, radiation exposure triggered the dissociation of these proteins so that Rad22 was stabilized and able to enhance HR.
authors.affiliation: Division of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida-konoecho, Sakyo-ku, Kyoto, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Jun
authors.initials: J
authors.lastname: Takeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
authors.forename: Junya
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kato
authors.forename: Kouji
authors.initials: K
authors.lastname: Hirota
authors.forename: Masato
authors.initials: M
authors.lastname: Taoka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Kenshi
authors.initials: K
authors.lastname: Komatsu
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Isobe
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000528:radiation effects; D059765:Homologous Recombination / Q000502:physiology* / Q000528:radiation effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C085412:rad52 protein, S pombe; D046988:Proteasome Endopeptidase Complex