BRCA2 in Abscission: Role in Cytokinesis and Recruitment of Abscission Regulators

The document reports on a study by Couch and colleagues which demonstrated that the tumor suppressor BRCA2 is involved in cytokinesis, specifically in the recruitment of abscission regulators to the midbody. The study used antibodies, siRNAs, and cells from BRCA2-knockout mice to confirm BRCA2's localization to the central spindle and midbody, and showed that its absence leads to cytokinesis failure. BRCA2's midbody localization was found to be dependent on its interaction with the actin-binding protein filamin A. In the absence of BRCA2, cytokinesis regulators such as MKLP1, MKLP2, PRC1, Alix, Tsg101, and endobrevin were mislocalized. Biochemical analyses indicated that BRCA2 promotes the formation of complexes between the abscission-regulator CEP55 and ESCRT-associated proteins Alix and Tsg101 during mitosis. The study also found that a BRCA2 deletion mutant lacking DNA repair function could still rescue cytokinesis defects, suggesting that BRCA2's roles in DNA repair and cytokinesis are separable. A specific BRCA2 missense mutation was identified that disrupts filamin A binding and midbody localization but retains DNA repair capacity, further supporting the separability of these functions. The potential implications of BRCA2's cytokinesis function in cancer remain an interesting area for future research.