{'fraction_non_alphanumeric': 0.021392454297938544, 'fraction_numerical': 0.0, 'mean_word_length': 5.561224489795919, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy

Significance Rapid detection of invasion of exogenous materials and subsequent responses are important for living organisms to survive hazards, such as pathogen infection. Understanding cellular responses against exogenous DNA provides clues not only for controlling pathogen infections that bring exogenous DNA into host cells, but also for designing efficient DNA delivery vectors for transgene expression. Here, by monitoring the invasion of exogenous DNA-coated polystyrene beads into living cells, we show that barrier-to-autointegration factor detects exogenous DNA immediately after its appearance at endosome breakdown and plays a role in DNA avoiding autophagy. These findings provide new insights into the mechanisms by which a cell detects and responds to exogenous double-stranded DNA. 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.