Cyclic GMP-AMP synthase recognizes the physical features of DNA  

作　　者：Ling Dong Yue-ru Hou Na Xu Xiao-qian Gao Zhen Sun Qing-kai Yang Li-na Wang 

机构地区：[1]Institute of Cancer Stem Cell,DaLian Medical University,Dalian,116044,China

出　　处：《Acta Pharmacologica Sinica》2025年第2期264-270,共7页中国药理学报(英文版)

基　　金：supported by grants from the National Natural Science Foundation of China(82173072).

摘　　要：Cyclic GMP-AMP synthase(cGAS)is a major cytosolic DNA sensor that plays a significant role in innate immunity.Upon binding to double stranded DNA(dsDNA),cGAS utilizes GTP and ATP to synthesize the second messenger cyclic GMP-AMP(cGAMP).The cGAMP then binds to the adapter protein stimulator of interferon genes(STING)in the endoplasmic reticulum,resulting in the activation of the transcription factor interferon regulatory factor 3(IRF3)and subsequent induction of type I interferon.An important question is how cGAS distinguishes between self and non-self DNA.While cGAS binds to the phosphate backbone of DNA without discrimination,its activation is influenced by physical features such as DNA length,inter-DNA distance,and mechanical flexibility.This suggests that the recognition of DNA by cGAS may depend on these physical features.In this article we summarize the recent progress in research on cGAS-STING pathway involved in antiviral defense,cellular senescence and anti-tumor response,and focus on DNA recognition mechanisms based on the physical features.

关 键 词：innate immune response cytosolic DNA sensor cyclic GMP-AMP synthase STING DNA physical features 

分 类 号：O62[理学—有机化学]