The tumour suppressor BRCA2 functions in DNA repair but has also been suggested to regulate cytokinesis. This role, however, as well as its localization at the midbody, has remained controversial. Couch and colleagues demonstrate that BRCA2 recruits regulators of abscission to the midbody (Dev. Cell 23, 137–152; 2012).

Using several antibodies, siRNAs (small interfering RNAs) and cells from BRCA2-knockout mice, the authors confirm that BRCA2 localizes to the central spindle and midbody, and that its loss causes cytokinesis failure. The midbody localization of BRCA2 is dependent on a previously identified interaction with the actin-binding protein filamin A. In the absence of BRCA2, cytokinesis regulators (such as MKLP1, MKLP2, PRC1, Alix, Tsg101 and endobrevin) are mislocalized, and biochemical analyses reveal that BRCA2 promotes the formation of complexes of the abscission-regulator CEP55 with ESCRT-associated proteins Alix and Tsg101 in mitosis. The authors thus propose that BRCA2 acts as a scaffold to assemble part of the cytokinesis machinery at the midbody. Importantly, a BRCA2 deletion mutant lacking DNA repair function is able to rescue cytokinesis defects induced by BRCA2 loss. The authors also identify a missense mutation in BRCA2 that disrupts filamin A binding and midbody localization but retains DNA repair capacity, showing that the functions are separable. Whether specific disruption of the cytokinesis function of BRCA2 plays a role in cancer is an interesting question for the future.