Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 339 (6121): 763-764

Copyright © 2013 by the American Association for the Advancement of Science

Sensing the Dark Side of DNA

Luke A. J. O'Neill

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland.


Figure 1
View larger version (70K):
[in this window]
[in a new window]

 
DNA sensor. (A) A well-characterized signaling pathway involves adenylate cyclase, which is activated by many hormones via G protein–coupled receptors (GPCRs) at the cell surface. Adenylate cyclase produces the second messenger molecule cAMP, which activates protein kinase A (PKA) and many cellular processes. (B) DNA from diverse microbes is sensed in the cytosol of infected cells as a danger signal. The cyclase cGAS binds this DNA, becomes catalytically active, and generates cGAMP as a second messenger. cGAMP binds to STING, which activates two signaling pathways that increase the expression of immune and inflammatory genes, thereby promoting host defense. The same process is likely to sense host DNA that leaks out of mitochondria or the nucleus in damaged cells, acting as a danger signal. Certain microbes make c-di-GMP or c-di-AMP, which activate STING; other microbes (and protozoa) can also synthesize cGAMP. How other DNA sensors fit into this process is unclear.

CREDIT: K. SUTLIFF/SCIENCE

 


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882