title: Rad52 inactivation is synthetically lethal with BRCA2 deficiency.
abstract: Synthetic lethality is a powerful approach to study selective cell killing based on genotype. We show that loss of Rad52 function is synthetically lethal with breast cancer 2, early onset (BRCA2) deficiency, whereas there was no impact on cell growth and viability in BRCA2-complemented cells. The frequency of both spontaneous and double-strand break-induced homologous recombination and ionizing radiation-induced Rad51 foci decreased by 2-10 times when Rad52 was depleted in BRCA2-deficient cells, with little to no effect in BRCA2-complemented cells. The absence of both Rad52 and BRCA2 resulted in extensive chromosome aberrations, especially chromatid-type aberrations. Ionizing radiation-induced and S phase-associated Rad52-Rad51 foci form equally well in the presence or absence of BRCA2, indicating that Rad52 can respond to DNA double-strand breaks and replication stalling independently of BRCA2. Rad52 thus is an independent and alternative repair pathway of homologous recombination and a target for therapy in BRCA2-deficient cells.
authors.affiliation: Department of Radiation Oncology, Washington University, St. Louis, MO 63108, USA.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Feng
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Scott
authors.forename: Wendy
authors.initials: W
authors.lastname: Bussen
authors.forename: Girdhar G
authors.initials: GG
authors.lastname: Sharma
authors.forename: Gongshe
authors.initials: G
authors.lastname: Guo
authors.forename: Tej K
authors.initials: TK
authors.lastname: Pandita
authors.forename: Simon N
authors.initials: SN
authors.lastname: Powell
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D051135:Rad51 Recombinase / Q000378:metabolism*; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D013778:Tetrazolium Salts; D013844:Thiazoles; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C022616:thiazolyl blue