Diverse cellular functions of barrier-to-autointegration factor and its roles in disease

Sears, Rhiannon M.; Roux, Kyle J.

doi:10.1242/jcs.246546

Cited by 33 publications

(37 citation statements)

References 130 publications

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“…This BAF-dependent NE assembly protects foreign DNA from autophagy 8,30 . Although BAF is expected to function as a defense against viral infection 29,75,76 , it unexpectedly assists in the integration of the human immunodeficiency virus (HIV) genome into the host genome by preventing the suicidal autointegration to the viral genome as named after barrier-to-autointegration factor 21,22 . In addition, a recent report showed that BAF protects against the cGAS-STING response to prevent innate immune activation 77,78 .…”

Section: Discussionmentioning

confidence: 99%

Transfected plasmid DNA is incorporated into the nucleus via nuclear envelope reformation at telophase

et al. 2022

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DNA transfection is an important technology in life sciences, wherein nuclear entry of DNA is necessary to express exogenous DNA. Non-viral vectors and their transfection reagents are useful as safe transfection tools. However, they have no effect on the transfection of non-proliferating cells, the reason for which is not well understood. This study elucidates the mechanism through which transfected DNA enters the nucleus for gene expression. To monitor the behavior of transfected DNA, we introduce plasmid bearing lacO repeats and RFP-coding sequences into cells expressing GFP-LacI and observe plasmid behavior and RFP expression in living cells. RFP expression appears only after mitosis. Electron microscopy reveals that plasmids are wrapped with nuclear envelope (NE)‒like membranes or associated with chromosomes at telophase. The depletion of BAF, which is involved in NE reformation, delays plasmid RFP expression. These results suggest that transfected DNA is incorporated into the nucleus during NE reformation at telophase.

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Section: Discussionmentioning

confidence: 99%

Transfected plasmid DNA is incorporated into the nucleus via nuclear envelope reformation at telophase

et al. 2022

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“…This BAFdependent NE assembly protects foreign DNA from autophagy 8,24 . Although BAF is expected to function as a defense against viral infection 23,57,58 , it unexpectedly assists in the integration of the human immunodeficiency virus (HIV) genome into the host genome 15,16 . In addition, a recent report showed that BAF protects against the cGAS-STING response to prevent innate immune activation 59,60 .…”

Section: Discussionmentioning

confidence: 99%

Transfected plasmid DNA is incorporated into the nucleus via nuclear envelope reformation at telophase

Haraguchi¹,

Koujin²,

Shindo³

et al. 2021

Preprint

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DNA transfection is an important technology in the life sciences, wherein nuclear entry of DNA is necessary to achieve expression of the exogenous DNA. Non-viral vectors and their transfection reagents are useful as safe tools for transfection. However, they have no effects for transfection of non-proliferating cells, the reason for which remains unknown. This study aimed to elucidate the mechanism by which transfected DNA enters the nucleus for gene expression. To monitor the intracellular behavior of transfected DNA, we introduced a plasmid bearing lacO repeats and RFP-coding sequences into cells expressing GFP-LacI and observed plasmid behavior and RFP expression. RFP expression appeared only after mitosis. Electron microscopy showed that plasmids were wrapped with nuclear envelope (NE)-like membranes or associated with chromosomes at telophase. Depletion of BAF, which is involved in NE reformation, delayed plasmid RFP expression. These results suggest that transfected DNA is incorporated into the nucleus via NE reformation at telophase.

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“…The present study raises novel perspectives for the characterization and design of BAF1-interacting small molecules. The discovery of BAF1 inhibitors is important because the protein plays a role in cancers and other human diseases ( Sears and Roux, 2020 ; Halfmann and Roux, 2021 ). Notably BAF1 plays roles in various viral diseases.…”

Section: Discussionmentioning

confidence: 99%

Interaction of obtusilactone B and related butanolide lactones with the barrier-to-autointegration factor 1 (BAF1). A computational study

Bailly

Vergoten

2021

Current Research in Pharmacology and Drug Discovery

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The barrier-to-autointegration factor 1 (BAF1) protein is a DNA-binding protein implicated in nuclear envelop repair and reformation after mitosis. This nuclear protein is frequently overexpressed in cancer cells and plays a role in the occurrence and development of different tumors. It is a potential therapeutic target for gastric cancer, breast cancer and other malignancies. For this reason, BAF1 inhibitors are searched. The butanolide lactone obtusilactone B (Ob-B) has been found to inhibit VRK1-dependent phosphorylation of BAF1, upon direct binding to the nuclear protein. Taking advantage of the known crystallographic structure of BAF1, we have elaborated molecular models of Ob-B bound to BAF1 to delimit the binding site and binding configuration. The long endoolefinic alkyl side chain of Ob-B extends into a small groove on the protein surface, and the adjacent exomethylene-γ-lactone moiety occupies a pocket comprising to the Ser-4 phosphorylation site of BAF1. Twenty butanolide lactones structurally close to ObB were screened for BAF1 binding. Several natural products with BAF1-binding capacity potentially superior to Ob-B were identified, including mahubanolide, kotomolide B, epilitsenolide D2, and a few other known anticancer plant natural products. Our study provides new ideas to guide the discovery and design of BAF1 inhibitors.

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Diverse cellular functions of barrier-to-autointegration factor and its roles in disease

Cited by 33 publications

References 130 publications

Transfected plasmid DNA is incorporated into the nucleus via nuclear envelope reformation at telophase

Transfected plasmid DNA is incorporated into the nucleus via nuclear envelope reformation at telophase

Transfected plasmid DNA is incorporated into the nucleus via nuclear envelope reformation at telophase

Interaction of obtusilactone B and related butanolide lactones with the barrier-to-autointegration factor 1 (BAF1). A computational study

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