BAF restricts cGAS on nuclear DNA to prevent innate immune activation

doi:10.1126/science.aaw6421

GSTDTAP > 气候变化

DOI	10.1126/science.aaw6421
	BAF restricts cGAS on nuclear DNA to prevent innate immune activation
	Baptiste Guey; Marilena Wischnewski; Alexiane Decout; Kristina Makasheva; Murat Kaynak; Mahmut S. Sakar; Beat Fierz; Andrea Ablasser
	2020-08-14
发表期刊	Science
出版年	2020
英文摘要	A signaling pathway in vertebrates called cGAS-STING detects the presence of intracellular DNA as a surrogate for both cellular damage and viral infection. At the same time, sensing of self-DNA must be suppressed to prevent the development of autoimmune responses. Guey et al. identify barrier-to-autointegration factor 1 (BAF) as a protein that intrinsically competes with the cGAS component of this pathway for binding to genomic self-DNA. When there is a breakdown in nuclear compartmentalization, cytosolic cGAS enzymatic activity is prevented because of BAF. This work suggests that the regulation of DNA detection by the innate immune system relies on more complex mechanisms than simple physical separation alone. Science , this issue p. [823][1] The appearance of DNA in the cytosol is perceived as a danger signal that stimulates potent immune responses through cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS). How cells regulate the activity of cGAS toward self-DNA and guard against potentially damaging autoinflammatory responses is a fundamental biological question. Here, we identify barrier-to-autointegration factor 1 (BAF) as a natural opponent of cGAS activity on genomic self-DNA. We show that BAF dynamically outcompetes cGAS for DNA binding, hence prohibiting the formation of DNA-cGAS complexes that are essential for enzymatic activity. Upon acute loss of nuclear membrane integrity, BAF is necessary to restrict cGAS activity on exposed DNA. Our observations reveal a safeguard mechanism, distinct from physical separation, by which cells protect themselves against aberrant immune responses toward genomic DNA. [1]: /lookup/doi/10.1126/science.aaw6421
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/288088
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Baptiste Guey,Marilena Wischnewski,Alexiane Decout,et al. BAF restricts cGAS on nuclear DNA to prevent innate immune activation[J]. Science,2020.
APA	Baptiste Guey.,Marilena Wischnewski.,Alexiane Decout.,Kristina Makasheva.,Murat Kaynak.,...&Andrea Ablasser.(2020).BAF restricts cGAS on nuclear DNA to prevent innate immune activation.Science.
MLA	Baptiste Guey,et al."BAF restricts cGAS on nuclear DNA to prevent innate immune activation".Science (2020).