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Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):7027-32. doi: 10.1073/pnas.1501235112. Epub 2015 May 19.

BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy.

Author information

1
Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, Nishi-ku, Kobe 651-2492, Japan;
2
Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, Nishi-ku, Kobe 651-2492, Japan; Laboratory of Electron Microscopy, Faculty of Science, Japan Women's University, Bunkyo-ku, Tokyo 112-8681, Japan;
3
Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, Nishi-ku, Kobe 651-2492, Japan; Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; Graduate School of Science, Osaka University, Toyonaka 560-0043, Japan.
4
Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, Nishi-ku, Kobe 651-2492, Japan; Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; Graduate School of Science, Osaka University, Toyonaka 560-0043, Japan tokuko@nict.go.jp.

Abstract

Knowledge of the mechanisms by which a cell detects exogenous DNA is important for controlling pathogen infection, because most pathogens entail the presence of exogenous DNA in the cytosol, as well as for understanding the cell's response to artificially transfected DNA. The cellular response to pathogen invasion has been well studied. However, spatiotemporal information of the cellular response immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is lacking, in part because of difficulties in monitoring when exogenous dsDNA enters the cytosol of the cell. We have recently developed a method to monitor endosome breakdown around exogenous materials using transfection reagent-coated polystyrene beads incorporated into living human cells as the objective for microscopic observations. In the present study, using dsDNA-coated polystyrene beads (DNA-beads) incorporated into living cells, we show that barrier-to-autointegration factor (BAF) bound to exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown. The BAF(+) DNA-beads then assembled a nuclear envelope (NE)-like membrane and avoided autophagy that targeted the remnants of the endosome membranes. Knockdown of BAF caused a significant decrease in the assembly of NE-like membranes and increased the formation of autophagic membranes around the DNA-beads, suggesting that BAF-mediated assembly of NE-like membranes was required for the DNA-beads to evade autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like membranes and avoided autophagy. We propose a new role for BAF: remodeling intracellular membranes upon detection of dsDNA in mammalian cells.

KEYWORDS:

DNA sensor; DNA-bead; autophagy; barrier-to-autointegration factor; nuclear envelope

PMID:
25991860
PMCID:
PMC4460496
DOI:
10.1073/pnas.1501235112
[Indexed for MEDLINE]
Free PMC Article

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