title: NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control.
abstract: The ability to sense and respond to DNA damage is critical to maintenance of genomic stability and the prevention of cancer. In this study, we employed a genetic screen to identify a gene, NBA1 (new component of the BRCA1 A complex), that is required for resistance to ionizing radiation. The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control. Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. NBA1 is required to maintain BRE and Abra1 abundance and for the recruitment of BRCA1 to sites of DNA damage. In depth bioinformatics analysis revealed that the BRCA1 A complex bears striking similarities to the 19S proteasome complex. Furthermore, we show that four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability, thus forming a complex that might facilitate the deubiquitinating activity of the deubiquitination enzyme BRCC36 or the E3 ligase activity of the BRCA1/BARD1 ligase. These findings provide a new perspective from which to view the BRCA1 A complex.
authors.affiliation: Department of Genetics, Howard Hughes Medical Institute, Center for Genetics and Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Kristen
authors.initials: K
authors.lastname: Hurov
authors.forename: Kay
authors.initials: K
authors.lastname: Hofmann
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D000072017:Deubiquitinating Enzymes; D006801:Humans; D007834:Lasers; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C540398:BABAM1 protein, human; D019313:BRCA1 Protein; D002352:Carrier Proteins; D008565:Membrane Proteins; D025821:Polyubiquitin; C518017:BRCC3 protein, human; D000072017:Deubiquitinating Enzymes; D046988:Proteasome Endopeptidase Complex