Authors:
CJ Vandenberg, F Gergely, CY Ong, P Pace, DL Mallery, K Hiom, KJ Patel
Journal name: 
Mol Cell
Citation info: 
12(1):247-254
Abstract: 
Monoubiquitination of the FANCD2 protein is a key step in the Fanconi anemia (FA) tumor suppressor pathway, coinciding with this molecule's accumulation at sites of genome damage. Strong circumstantial evidence points to a requirement for the BRCA1 gene product in this step. Here, we show that the purified BRCA1/BARD1 complex, together with E1 and UbcH5a, is sufficient to reconstitute the monoubiquitination of FANCD2 in vitro. Although siRNA-mediated knockdown of BRCA1 in human cells results in defective targeting of FANCD2 to sites of DNA damage, it does not lead to a defect in FANCD2 ubiquitination. Furthermore, ablation of the RING finger domains of either BRCA1 or BARD1 in the chicken B cell line DT40 also leaves FANCD2 modification intact. Consequently, while BRCA1 affects the accumulation of FANCD2 at sites of DNA damage, BRCA1/BARD1 E3 ligase activity is not essential for the monoubiquitination of FANCD2.
DOI: 
http://doi.org/10.1016/s1097-2765(03)00281-8
Research group: 
Gergely Group
E-pub date: 
01 Jul 2003
Users with this publication listed: 
Fanni Gergely