BRCA2 Localization to the Midbody by Filamin A Regulates CEP55 Signaling and Completion of Cytokinesis

Gourish Mondal, Matthew Rowley, Lucia Guidugli, Jianmin Wu, Vernon S. Pankratz, Fergus J. Couch

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)137-152
Number of pages16
JournalDevelopmental Cell
Volume23
Issue number1
DOIs
StatePublished - Jul 17 2012

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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