(722b) Repair of Nuclear Rupture during Cell Migration Requires Barrier-to-Autointegration Factor

Authors: 
Lele, T., University of Florida
Roux, K., Sanford Children's Health Research Center
Halfmann, C., Sanford Research
Sears, R., Sanford Research
Aman, L., Sanford Research
Angelini, T., University of Florida
O'Bryan, C., University of Florida
Zhang, Q., University of Florida
Katiyar, A., University of Florida
Upon exposure to mechanical forces during cell migration, cell nuclei rupture, breaking the nucleo-cytoplasmic barrier and exposing the genome to cytosolic constituents. This nuclear rupture can lead to DNA damage and activation of innate immune signaling, but it is often repairable. BAF is a small cytoplasmic and nuclear DNA-binding protein that has roles in innate immunity and nuclear envelope reformation, and has been shown to target to sites of nuclear rupture. Here, we show that it is predominantly the cytoplasmic population of BAF that localizes to these nuclear ruptures in a DNA-dependent manner. BAF affinity to transmembrane LEM-domain proteins subsequently leads to their accumulation at rupture sites. Loss of BAF inhibits recruitment of these LEM-domain proteins and membranes to the sites of nuclear ruptures and prevents the functional resealing of the ruptured nuclear envelope. Thus, BAF is a critical component of the cellular response to nuclear rupture.