Anti-cGAS antibody

Target data

Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed : 21478870, PubMed : 23258413, PubMed : 23707061, PubMed : 23707065, PubMed : 23722159, PubMed : 24077100, PubMed : 24116191, PubMed : 24462292, PubMed : 25131990, PubMed : 26300263, PubMed : 29976794, PubMed : 30799039, PubMed : 31142647, PubMed : 32814054, PubMed : 33273464, PubMed : 33542149, PubMed : 37217469, PubMed : 37802025). Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p] (PubMed : 28214358, PubMed : 28363908). Acts as a key DNA sensor : directly binds double-stranded DNA (dsDNA), inducing the formation of liquid-like droplets in which CGAS is activated, leading to synthesis of 2',3'-cGAMP, a second messenger that binds to and activates STING1, thereby triggering type-I interferon production (PubMed : 28314590, PubMed : 28363908, PubMed : 29976794, PubMed : 32817552, PubMed : 33230297, PubMed : 33606975, PubMed : 35322803, PubMed : 35438208, PubMed : 35460603, PubMed : 35503863). Preferentially recognizes and binds curved long dsDNAs of a minimal length of 40 bp (PubMed : 30007416). Acts as a key foreign DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses (PubMed : 28363908). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed : 28363908, PubMed : 35613581). Also acts as an innate immune sensor of infection by retroviruses, such as HIV-2, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed : 23929945, PubMed : 24269171, PubMed : 30270045, PubMed : 32852081). In contrast, HIV-1 is poorly sensed by CGAS, due to its capsid that cloaks viral DNA from CGAS detection (PubMed : 24269171, PubMed : 30270045, PubMed : 32852081). Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA (PubMed : 26046437). Also detects the presence of DNA from bacteria, such as M.tuberculosis (PubMed : 26048138). 2',3'-cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote STING1 activation and convey immune response to connecting cells (PubMed : 24077100, PubMed : 31992625). 2',3'-cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but STING1-dependent manner (PubMed : 26229115). Also senses the presence of neutrophil extracellular traps (NETs) that are translocated to the cytosol following phagocytosis, leading to synthesis of 2',3'-cGAMP (PubMed : 33688080). In addition to foreign DNA, can also be activated by endogenous nuclear or mitochondrial DNA (PubMed : 28738408, PubMed : 28759889, PubMed : 31299200, PubMed : 33031745, PubMed : 33230297). When self-DNA leaks into the cytosol during cellular stress (such as mitochondrial stress, SARS-CoV-2 infection causing severe COVID-19 disease, DNA damage, mitotic arrest or senescence), or is present in form of cytosolic micronuclei, CGAS is activated leading to a state of sterile inflammation (PubMed : 28738408, PubMed : 28759889, PubMed : 31299200, PubMed : 33031745, PubMed : 33230297, PubMed : 35045565). Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via STING1 and promote cellular senescence (By similarity). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks : acts by localizing to micronuclei arising from genome instability (PubMed : 28738408, PubMed : 28759889). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane : following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to 2',3'-cGAMP synthesis and subsequent activation of STING1 and type-I interferon production (PubMed : 28738408, PubMed : 28759889). Activated in response to prolonged mitotic arrest, promoting mitotic cell death (PubMed : 31299200). In a healthy cell, CGAS is however kept inactive even in cellular events that directly expose it to self-DNA, such as mitosis, when cGAS associates with chromatin directly after nuclear envelope breakdown or remains in the form of postmitotic persistent nuclear cGAS pools bound to chromatin (PubMed : 31299200, PubMed : 33542149). Nuclear CGAS is inactivated by chromatin via direct interaction with nucleosomes, which block CGAS from DNA binding and thus prevent CGAS-induced autoimmunity (PubMed : 31299200, PubMed : 32911482, PubMed : 32912999, PubMed : 33051594, PubMed : 33542149). Also acts as a suppressor of DNA repair in response to DNA damage : inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex (PubMed : 30356214, PubMed : 31544964). In addition to DNA, also sense translation stress : in response to translation stress, translocates to the cytosol and associates with collided ribosomes, promoting its activation and triggering type-I interferon production (PubMed : 34111399). In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less 2',3'-cGAMP, allowing a more fine-tuned response to pathogens (PubMed : 30007416).