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J Cell Biol. 2019 Jul 1;218(7):2136-2149. doi: 10.1083/jcb.201901116. Epub 2019 May 30.

Repair of nuclear ruptures requires barrier-to-autointegration factor.

Author information

1
Enabling Technologies Group, Sanford Research, Sioux Falls, SD.
2
Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD.
3
Department of Chemical Engineering, University of Florida, Gainesville, FL.
4
Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL.
5
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL.
6
Institute for Cell and Tissue Science and Engineering, University of Florida, Gainesville, FL.
7
Enabling Technologies Group, Sanford Research, Sioux Falls, SD kyle.roux@sanfordhealth.org.
8
Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD.

Abstract

Cell nuclei rupture following exposure to mechanical force and/or upon weakening of nuclear integrity, but nuclear ruptures are repairable. Barrier-to-autointegration factor (BAF), a small DNA-binding protein, rapidly localizes to nuclear ruptures; however, its role at these rupture sites is unknown. Here, we show that it is predominantly a nonphosphorylated cytoplasmic population of BAF that binds nuclear DNA to rapidly and transiently localize to the sites of nuclear rupture, resulting in BAF accumulation in the nucleus. BAF subsequently recruits transmembrane LEM-domain proteins, causing their accumulation at rupture sites. Loss of BAF impairs recruitment of LEM-domain proteins and nuclear envelope membranes to nuclear rupture sites and prevents nuclear envelope barrier function restoration. Simultaneous depletion of multiple LEM-domain proteins similarly inhibits rupture repair. LEMD2 is required for recruitment of the ESCRT-III membrane repair machinery to ruptures; however, neither LEMD2 nor ESCRT-III is required to repair ruptures. These results reveal a new role for BAF in the response to and repair of nuclear ruptures.

PMID:
31147383
PMCID:
PMC6605789
[Available on 2020-01-01]
DOI:
10.1083/jcb.201901116

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