PT  - JOURNAL ARTICLE
AU  - Brittany L Uhlorn
AU  - Eduardo R Gamez
AU  - Shuaizhi Li
AU  - Samuel K Campos
TI  - Attenuation of cGAS/STING activity during mitosis
AID  - 10.26508/lsa.201900636
DP  - 2020 Sep 01
TA  - Life Science Alliance
PG  - e201900636
VI  - 3
IP  - 9
4099  - https://www.life-science-alliance.org/content/3/9/e201900636.short
4100  - https://www.life-science-alliance.org/content/3/9/e201900636.full
SO  - Life Sci. Alliance2020 Sep 01; 3
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.