Identification of Filamin A As a BRCA1-interacting Protein Required for Efficient DNA Repair

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2010 Mar 23

PMID 20305393

Citations 29

Authors

Aneliya Velkova

Marcelo A Carvalho

Joseph O Johnson

Sean V Tavtigian

Alvaro N A Monteiro

Affiliations

Soon will be listed here.

Abstract

The product of the breast and ovarian cancer susceptibility gene BRCA1 has been implicated in several aspects of the DNA damage response but its biochemical function in these processes has remained elusive. In order to probe BRCA1 function we conducted a yeast two-hybrid screening to identify interacting partners to a conserved motif (Motif 6) in the central region of BRCA1. Here we report the identification of the actin-binding protein Filamin A (FLNA) as BRCA1 partner and demonstrate that FLNA is required for efficient regulation of early stages of DNA repair processes. Cells lacking FLNA display a diminished BRCA1 IR-induced focus formation and a delayed kinetics of Rad51 focus formation. In addition, our data also demonstrate that FLNA is required to stabilize the interaction between components of the DNA-PK holoenzyme, DNA-PKcs and Ku86 in a BRCA1-independent fashion. Our data is consistent with a model in which absence of FLNA compromises homologous recombination and non-homologous end joining. Our findings have implications for the response to irradiation induced DNA damage.

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