{"entity": "publication", "iuid": "be29d64ad41d4383965eafc73608cac4", "timestamp": "2026-08-29T04:15:59.503Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/be29d64ad41d4383965eafc73608cac4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/be29d64ad41d4383965eafc73608cac4"}}, "title": "Cyanobacterial Argonautes and Cas4 family nucleases cooperate to interfere with invading DNA.", "authors": [{"family": "Bobadilla Ugarte", "given": "Pilar", "initials": "P"}, {"family": "Halter", "given": "Stefanie", "initials": "S"}, {"family": "Mutte", "given": "Sumanth K", "initials": "SK"}, {"family": "Heijstek", "given": "Clint", "initials": "C"}, {"family": "Niault", "given": "Theophile", "initials": "T"}, {"family": "Terenin", "given": "Ilya", "initials": "I"}, {"family": "Barendse", "given": "Patrick", "initials": "P"}, {"family": "Koopal", "given": "Balwina", "initials": "B"}, {"family": "Roosjen", "given": "Mark", "initials": "M"}, {"family": "Boeren", "given": "Sjef", "initials": "S"}, {"family": "Hauryliuk", "given": "Vasili", "initials": "V"}, {"family": "Jinek", "given": "Martin", "initials": "M"}, {"family": "Westphal", "given": "Adrie H", "initials": "AH"}, {"family": "Swarts", "given": "Daan C", "initials": "DC"}], "type": "journal article", "published": "2025-05-15", "journal": {"title": "Mol. Cell", "issn": "1097-4164", "volume": "85", "issue": "10", "pages": "1920-1937.e10", "issn-l": "1097-2765"}, "abstract": "Prokaryotic Argonaute proteins (pAgos) from the long-A clade are stand-alone immune systems that use small interfering DNA (siDNA) guides to recognize and cleave invading plasmid and virus DNA. Certain long-A pAgos are co-encoded with accessory proteins with unknown functions. Here, we show that cyanobacterial long-A pAgos act in conjunction with Argonaute-associated Cas4 family enzyme 1 (ACE1). Structural and biochemical analyses reveal that ACE1-associated pAgos mediate siDNA-guided DNA interference, akin to stand-alone pAgos. ACE1 is structurally homologous to the nuclease domain of bacterial DNA repair complexes and acts as a single-stranded DNA endonuclease that processes siDNA guides. pAgo and ACE1 form a heterodimeric long-A pAgo-ACE1 (APACE1) complex, which modulates ACE1 activity. Although ACE1-associated pAgos alone interfere with plasmids and bacteriophages, plasmid interference is boosted when pAgo and ACE1 are co-expressed. Our study reveals that pAgo-mediated immunity is enhanced by accessory proteins and broadens our mechanistic understanding of how pAgo systems interfere with invading DNA.", "doi": "10.1016/j.molcel.2025.03.025", "pmid": "40288374", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12094033"}, {"db": "pii", "key": "S1097-2765(25)00302-8"}], "notes": [], "created": "2026-08-21T11:25:46.097Z", "modified": "2026-08-21T11:25:46.111Z"}