biostudies-literatureLiang QNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSe4374https://www.ebi.ac.uk/biostudies/studies/S-EPMC9214754biostudies-literatureUnknown31(7)The widespread CBASS (cyclic oligonucleotide-based anti-phage signaling system) immune systems in bacteria protect their hosts from bacteriophage infection by triggering programmed cell death. CBASS systems all encode a cyclic oligonucleotide synthase related to eukaryotic cGAS but use diverse regulators and effector proteins including nucleases, phospholipases, and membrane-disrupting proteins to effect cell death. Cap18 is a predicted 3'-5' exonuclease associated with hundreds of CBASS systems, whose structure, biochemical activities, and biological roles remain unknown. Here we show that Cap18 is a DEDDh-family exonuclease related to the bacterial exonucleases RNase T and Orn and has nonspecific 3'-5' DNA exonuclease activity. Cap18 is commonly found in CBASS systems with associated CapProtein science : a publication of the Protein SocietyStructure and activity of a bacterial defense-associated 3'-5' exonuclease.PMC9214754T32 GM008326F31 GM137600R21 AI148814T32 GM127235R35 GM144121Ye QLau RKUr SNLiang QCorbett KDRichey STfalseStructure and activity of a bacterial defense-associated 3'-5' exonuclease.The widespread CBASS (cyclic oligonucleotide-based anti-phage signaling system) immune systems in bacteria protect their hosts from bacteriophage infection by triggering programmed cell death. CBASS systems all encode a cyclic oligonucleotide synthase related to eukaryotic cGAS but use diverse regulators and effector proteins including nucleases, phospholipases, and membrane-disrupting proteins to effect cell death. Cap18 is a predicted 3'-5' exonuclease associated with hundreds of CBASS systems, whose structure, biochemical activities, and biological roles remain unknown. Here we show that Cap18 is a DEDDh-family exonuclease related to the bacterial exonucleases RNase T and Orn and has nonspecific 3'-5' DNA exonuclease activity. Cap18 is commonly found in CBASS systems with associated Cap2022-01-01T00:00:00Z2022 Jul2026-04-08T11:48:25.771Z2024-10-16T15:23:06.929ZS-EPMC92147543576272710.1002/pro.4374