RT Journal Article
SR Electronic
T1 Attenuation of cGAS/STING activity during mitosis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900636
DO 10.26508/lsa.201900636
VO 3
IS 9
A1 Brittany L Uhlorn
A1 Eduardo R Gamez
A1 Shuaizhi Li
A1 Samuel K Campos
YR 2020
UL https://www.life-science-alliance.org/content/3/9/e201900636.abstract
AB The innate immune system recognizes cytosolic DNA associated with microbial infections and cellular stress via the cGAS/STING pathway, leading to activation of phospho-IRF3 and downstream IFN-I and senescence responses. To prevent hyperactivation, cGAS/STING is presumed to be nonresponsive to chromosomal self-DNA during open mitosis, although specific regulatory mechanisms are lacking. Given a role for the Golgi in STING activation, we investigated the state of the cGAS/STING pathway in interphase cells with artificially vesiculated Golgi and in cells arrested in mitosis. We find that whereas cGAS activity is impaired through interaction with mitotic chromosomes, Golgi integrity has little effect on the enzyme’s production of cGAMP. In contrast, STING activation in response to either foreign DNA (cGAS-dependent) or exogenous cGAMP is impaired by a vesiculated Golgi. Overall, our data suggest a secondary means for cells to limit potentially harmful cGAS/STING responses during open mitosis via natural Golgi vesiculation.