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Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector

Author

Listed:
  • Olga Rechkoblit

    (Icahn School of Medicine at Mount Sinai)

  • Daniela Sciaky

    (Icahn School of Medicine at Mount Sinai)

  • Mi Ni

    (Icahn School of Medicine at Mount Sinai)

  • Yangmei Li

    (Icahn School of Medicine at Mount Sinai)

  • Jithesh Kottur

    (Icahn School of Medicine at Mount Sinai
    Institute of Advanced Virology)

  • Gang Fang

    (Icahn School of Medicine at Mount Sinai)

  • Aneel K. Aggarwal

    (Icahn School of Medicine at Mount Sinai)

Abstract

Bacterial CBASS immune defense systems commonly kill virally infected cells by degrading genomic DNA in a form of cell suicide or abortive infection. We present a high-resolution structure of the CBASS effector Cap5, activated by a cyclic nucleotide, in the act of digesting DNA via tetrameric HNH endonuclease domains. Two HNH domains are in a catalytically active state for cleavage of the DNA strands, whereas the other two HNH domains are in a topologically distinct catalytically inactive state for simply DNA binding. The four HNH domains track one face of the DNA and mark an enzyme that acts as a stand-alone non-specific nuclease. We also show that chromosomally encoded CBASS Cap5 can be extrinsically activated by a cyclic nucleotide, as a step towards potential antibiotics.

Suggested Citation

  • Olga Rechkoblit & Daniela Sciaky & Mi Ni & Yangmei Li & Jithesh Kottur & Gang Fang & Aneel K. Aggarwal, 2025. "Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60484-z
    DOI: 10.1038/s41467-025-60484-z
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    References listed on IDEAS

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    1. Yong Sheng & Hengyu Wang & Yixin Ou & Yingying Wu & Wei Ding & Meifeng Tao & Shuangjun Lin & Zixin Deng & Linquan Bai & Qianjin Kang, 2023. "Insertion sequence transposition inactivates CRISPR-Cas immunity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Karen E. Flick & Melissa S. Jurica & Raymond J. Monnat & Barry L. Stoddard, 1998. "DNA binding and cleavage by the nuclear intron-encoded homing endonuclease I-PpoI," Nature, Nature, vol. 394(6688), pages 96-101, July.
    3. Rutger D. Luteijn & Shivam A. Zaver & Benjamin G. Gowen & Stacia K. Wyman & Nick E. Garelis & Liberty Onia & Sarah M. McWhirter & George E. Katibah & Jacob E. Corn & Joshua J. Woodward & David H. Raul, 2019. "SLC19A1 transports immunoreactive cyclic dinucleotides," Nature, Nature, vol. 573(7774), pages 434-438, September.
    4. Benjamin R. Morehouse & Apurva A. Govande & Adi Millman & Alexander F. A. Keszei & Brianna Lowey & Gal Ofir & Sichen Shao & Rotem Sorek & Philip J. Kranzusch, 2020. "STING cyclic dinucleotide sensing originated in bacteria," Nature, Nature, vol. 586(7829), pages 429-433, October.
    5. Daniel Cohen & Sarah Melamed & Adi Millman & Gabriela Shulman & Yaara Oppenheimer-Shaanan & Assaf Kacen & Shany Doron & Gil Amitai & Rotem Sorek, 2019. "Cyclic GMP–AMP signalling protects bacteria against viral infection," Nature, Nature, vol. 574(7780), pages 691-695, October.
    6. Christian Biertümpfel & Wei Yang & Dietrich Suck, 2007. "Crystal structure of T4 endonuclease VII resolving a Holliday junction," Nature, Nature, vol. 449(7162), pages 616-620, October.
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