The article "cGAS Goes Viral: A Conserved Immune Defense System from Bacteria to Humans" explores the evolutionary conservation and functional roles of the cGAS (cyclic-GMP-AMP synthase) protein across various organisms, including bacteria, invertebrates, and humans. cGAS is a key sensor in the innate immune system that detects cytosolic DNA, which can originate from microbial infections, viral replication, or host DNA damage. Upon detecting double-stranded DNA (dsDNA), cGAS catalyzes the production of cyclic dinucleotides (CDNs), such as 2′3′-cGAMP, which activate the STING (stimulator of interferon genes) pathway. This signaling cascade leads to the production of type I interferons and pro-inflammatory responses, crucial for combating infections. The study highlights the broad conservation of cGAS-like signaling in eukaryotes and its presence in bacteria, where it forms part of the cyclic-oligonucleotide-based antiphage signaling systems (CBASS). These systems help bacteria defend against phage infections by producing second messengers that trigger cell death, thereby preventing phage propagation. The CBASS systems include various components, such as CD-NTase enzymes, which synthesize nucleotide second messengers, and effector proteins that induce cell death. These systems are often regulated by complex mechanisms involving multiple proteins and signaling pathways. In addition to its role in immune defense, cGAS signaling is involved in various physiological processes, including anti-cancer immunity, autoimmune diseases, and aging. The article also discusses the structural and functional diversity of cGAS homologs across different species, emphasizing the importance of understanding their activation mechanisms and regulatory features. The study underscores the significance of cGAS in both innate immunity and bacterial defense against viral infections, suggesting that the cGAS-STING pathway may have evolutionary origins in prokaryotes. Overall, the research provides a comprehensive overview of the cGAS signaling pathway and its role in immune defense across a wide range of organisms.The article "cGAS Goes Viral: A Conserved Immune Defense System from Bacteria to Humans" explores the evolutionary conservation and functional roles of the cGAS (cyclic-GMP-AMP synthase) protein across various organisms, including bacteria, invertebrates, and humans. cGAS is a key sensor in the innate immune system that detects cytosolic DNA, which can originate from microbial infections, viral replication, or host DNA damage. Upon detecting double-stranded DNA (dsDNA), cGAS catalyzes the production of cyclic dinucleotides (CDNs), such as 2′3′-cGAMP, which activate the STING (stimulator of interferon genes) pathway. This signaling cascade leads to the production of type I interferons and pro-inflammatory responses, crucial for combating infections. The study highlights the broad conservation of cGAS-like signaling in eukaryotes and its presence in bacteria, where it forms part of the cyclic-oligonucleotide-based antiphage signaling systems (CBASS). These systems help bacteria defend against phage infections by producing second messengers that trigger cell death, thereby preventing phage propagation. The CBASS systems include various components, such as CD-NTase enzymes, which synthesize nucleotide second messengers, and effector proteins that induce cell death. These systems are often regulated by complex mechanisms involving multiple proteins and signaling pathways. In addition to its role in immune defense, cGAS signaling is involved in various physiological processes, including anti-cancer immunity, autoimmune diseases, and aging. The article also discusses the structural and functional diversity of cGAS homologs across different species, emphasizing the importance of understanding their activation mechanisms and regulatory features. The study underscores the significance of cGAS in both innate immunity and bacterial defense against viral infections, suggesting that the cGAS-STING pathway may have evolutionary origins in prokaryotes. Overall, the research provides a comprehensive overview of the cGAS signaling pathway and its role in immune defense across a wide range of organisms.