title: RAP80 protein is important for genomic stability and is required for stabilizing BRCA1-A complex at DNA damage sites in vivo.
abstract: RAP80 (receptor-associated protein 80) is a ubiquitin-binding protein that can specifically recognize and bind to Lys-63-linked polyubiquitin chains, thus targeting the BRCA1-A complex to DNA damage sites. To study the role of RAP80 in vivo, we generated RAP80-deficient mice. The deficient mice are prone to B-cell lymphomagenesis. B-cell lymphomas in RAP80-deficient mice are nearly diploid but harbor clonal chromosome translocations. Moreover, the deficient mice are hypersensitive to ionizing radiation. Repair of ionizing radiation-induced DNA double-strand breaks is impaired in RAP80-deficient mouse embryonic fibroblasts. Mechanistically, loss of RAP80 suppresses recruitment of the BRCA1-A complex to DNA damage sites and abrogates the DNA damage repair process at DNA damage sites. Taken together, these results reveal that RAP80 plays a crucial role in the DNA damage response and in maintaining genomic integrity.
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Jiaxue
authors.initials: J
authors.lastname: Wu
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D019313:BRCA1 Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D042822:Genomic Instability / Q000502:physiology*; D056488:Histone Chaperones; D051379:Mice; D018345:Mice, Knockout; D011817:Rabbits; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000906:Antibodies; D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C543502:Rap80 protein, mouse; D014157:Transcription Factors; D025801:Ubiquitin