Journal of the American Chemical Society

How a DNA Signal Activates the CRISPR-Cas9 System

Updated

Abstract

PAM recognition induces an allosteric mechanism in Cas9 that facilitates DNA cleavage.

  • PAM binding is crucial for the Cas9 endonuclease to generate double strand breaks in DNA.
  • Microsecond molecular dynamics simulations provide evidence for the allosteric mechanism activated by PAM.
  • PAM functions as an allosteric effector, influencing the conformational changes in the Cas9 catalytic domains.
  • The interdependent dynamics of the HNH and RuvC domains are essential for the coordinated cleavage of both DNA strands.
  • Targeting this allosteric mechanism may offer a way to control the functionality of CRISPR-Cas9.

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