NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control
- 1Department of Genetics, Howard Hughes Medical Institute, Center for Genetics and Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 2Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA;
- 3Miltenyi Biotec GmbH, 51429 Bergisch-Gladbach, Germany
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.
Keywords
Footnotes
-
↵4 Corresponding author.
↵E-MAIL selledge{at}genetics.med.harvard.edu; FAX (617) 525-4500.
-
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1770309.
-
Supplemental material is available at http://www.genesdev.org.
-
- Received December 8, 2008.
- Accepted February 2, 2009.
-
Freely available online through the Genes & Development Open Access option.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press