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Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease

Author

Listed:
  • Carolin Anders

    (University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland)

  • Ole Niewoehner

    (University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland)

  • Alessia Duerst

    (University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland)

  • Martin Jinek

    (University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland)

Abstract

Crystal structure of the RNA-guided endonuclease Cas9 bound to a guide RNA and a target DNA duplex reveals how base-specific recognition of a short motif known as PAM in the DNA target results in localized strand separation in the DNA immediately upstream of the PAM, allowing the target DNA strand to hybridize to the guide RNA.

Suggested Citation

  • Carolin Anders & Ole Niewoehner & Alessia Duerst & Martin Jinek, 2014. "Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease," Nature, Nature, vol. 513(7519), pages 569-573, September.
    • Handle: RePEc:nat:nature:v:513:y:2014:i:7519:d:10.1038_nature13579
    DOI: 10.1038/nature13579
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    Cited by:

    1. Kazuki Kato & Sae Okazaki & Soumya Kannan & Han Altae-Tran & F. Esra Demircioglu & Yukari Isayama & Junichiro Ishikawa & Masahiro Fukuda & Rhiannon K. Macrae & Tomohiro Nishizawa & Kira S. Makarova & , 2022. "Structure of the IscB–ωRNA ribonucleoprotein complex, the likely ancestor of CRISPR-Cas9," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Yang Liu & Filipe Pinto & Xinyi Wan & Zhugen Yang & Shuguang Peng & Mengxi Li & Jonathan M. Cooper & Zhen Xie & Christopher E. French & Baojun Wang, 2022. "Reprogrammed tracrRNAs enable repurposing of RNAs as crRNAs and sequence-specific RNA biosensors," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Shiran Abadi & Winston X Yan & David Amar & Itay Mayrose, 2017. "A machine learning approach for predicting CRISPR-Cas9 cleavage efficiencies and patterns underlying its mechanism of action," PLOS Computational Biology, Public Library of Science, vol. 13(10), pages 1-24, October.
    4. Behrouz Eslami-Mossallam & Misha Klein & Constantijn V. D. Smagt & Koen V. D. Sanden & Stephen K. Jones & John A. Hawkins & Ilya J. Finkelstein & Martin Depken, 2022. "A kinetic model predicts SpCas9 activity, improves off-target classification, and reveals the physical basis of targeting fidelity," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Dalton T. Ham & Tyler S. Browne & Pooja N. Banglorewala & Tyler L. Wilson & Richard K. Michael & Gregory B. Gloor & David R. Edgell, 2023. "A generalizable Cas9/sgRNA prediction model using machine transfer learning with small high-quality datasets," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Jian Wang & Yuxi Teng & Ruihua Zhang & Yifei Wu & Lei Lou & Yusong Zou & Michelle Li & Zhong-Ru Xie & Yajun Yan, 2021. "Engineering a PAM-flexible SpdCas9 variant as a universal gene repressor," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    7. Sundaram Acharya & Asgar Hussain Ansari & Prosad Kumar Das & Seiichi Hirano & Meghali Aich & Riya Rauthan & Sudipta Mahato & Savitri Maddileti & Sajal Sarkar & Manoj Kumar & Rhythm Phutela & Sneha Gul, 2024. "PAM-flexible Engineered FnCas9 variants for robust and ultra-precise genome editing and diagnostics," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    8. Grace N. Hibshman & Jack P. K. Bravo & Matthew M. Hooper & Tyler L. Dangerfield & Hongshan Zhang & Ilya J. Finkelstein & Kenneth A. Johnson & David W. Taylor, 2024. "Unraveling the mechanisms of PAMless DNA interrogation by SpRY-Cas9," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Eman A. Ageely & Ramadevi Chilamkurthy & Sunit Jana & Leonora Abdullahu & Daniel O’Reilly & Philip J. Jensik & Masad J. Damha & Keith T. Gagnon, 2021. "Gene editing with CRISPR-Cas12a guides possessing ribose-modified pseudoknot handles," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    10. Adeeb Rahman & Neeti Sanan-Mishra, 2024. "When an Intruder Comes Home: GM and GE Strategies to Combat Virus Infection in Plants," Agriculture, MDPI, vol. 14(2), pages 1-26, February.

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