Disruption of the BRCA2 tumor suppressor is associated with structural and numerical chromosomal defects. The numerical abnormalities in BRCA2-deficient cells may partly result from aberrations in cell division caused by disruption of BRCA2 during cytokinesis. Here we show that BRCA2 is a component of the midbody that is recruited through an interaction with Filamin A actin-binding protein. At the midbody, BRCA2 influences the recruitment of endosomal sorting complex required for transport (ESCRT)-associated proteins, Alix and Tsg101, and formation of CEP55-Alix and CEP55-Tsg101 complexes during abscission. Disruption of these BRCA2 interactions by cancer-associated mutations results in increased cytokinetic defects but has no effect on BRCA2-dependent homologous recombination repair of DNA damage. These findings identify a specific role for BRCA2 in the regulation of midbody structure and function, separate from DNA damage repair, that may explain in part the whole-chromosomal instability in BRCA2-deficient tumors. © 2012 Elsevier Inc.
Mondal, G., Rowley, M., Guidugli, L., Wu, J., Pankratz, V. S., & Couch, F. J. (2012). BRCA2 Localization to the Midbody by Filamin A Regulates CEP55 Signaling and Completion of Cytokinesis. Developmental Cell, 23(1), 137–152. https://doi.org/10.1016/j.devcel.2012.05.008