A Conserved Phage Recombinant System Counters Host CRISPR Immunity

A Conserved Phage Recombinant System Counters Host CRISPR Immunity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A Conserved Phage Recombinant System Counters Host CRISPR Immunity Yingfei Ma, Heng Zhu, Shengkun Dai, Shifeng Hou, Yuelong Li, Xin TAN, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5972272/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The discovery of CRISPR-Cas systems and their antagonistic anti-CRISPR proteins (Acrs) exemplifies the perpetual arms race between bacteria and phages. While bacterial CRISPR-Cas systems function as adaptive immune mechanisms to combat phage infection, phages have evolved counterstrategies, such as various Acrs that disrupt CRISPR-mediated immunity via diverse molecular pathways. Here, we report the identification of a phage-encoded multi-protein system conferring anti-type I-F CRISPR activity. This system consists of three functionally distinct proteins: a RecA ATPase (SSAP), a DUF669 domain-containing protein (SSB), and a RecB exonuclease (Exo). Our mechanistic analysis reveals that SSB acts as a first-response mediator, forming a polymeric assembly to specifically binding to the Csy_dsDNA R-LOOP structure. This interaction creates a molecular platform enabling the coordinated recruitment of SSAP and Exo, which collectively execute homologous recombination-mediated repair of CRISPR-induced phage DNA break. These findings establish a paradigm of multi-protein synergy in phage counter-defense strategies, advancing our understanding of the intricate evolutionary dynamics in host-phage conflicts. Biological sciences/Microbiology/Phage biology Biological sciences/Molecular biology/DNA recombination Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementarytablesNMICROBIOL25020446.rar Dataset 1 extendeddataNMICROBIOL25020446.rar Dataset 2 supplementaryFig.S5.gif Supplementary Fig. 5: The predicted structures AF3pred_Csy_dsDNA_Gp63(2). Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5972272","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":415944288,"identity":"f5e642e6-5470-4ef4-a53a-2d37a00664d5","order_by":0,"name":"Yingfei 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