2024/01/11 by Qiao Lu, Simone Pigolotti, Lu, Qiao +1
Biochemistry, Genetics and Molecular Biology · #Advanced biosensing and bioanalysis techniques #Biomolecules (q-bio.BM) #CRISPR and Genetic Engineering #Diffusion and Search Dynamics #FOS: Biological sciences #Subcellular Processes (q-bio.SC)
paper · pdf · doi:10.48550/arxiv.2401.05714
openalex publication_date 2024/01/11 · openalex created_date 2024/01/13 · openalex updated_date 2026/07/28
We study how Cas9, a central component of the CRISPR/Cas9 system, searches for a target sequence on the DNA. We propose a model that includes as key ingredients 3D diffusion, 1D sliding along the DNA, and the effect of short binding sequences preceding the target (protospacer adjacent sequences -- PAMs). This latter aspect constitutes the main difference with traditional facilitated diffusion of transcription factors. We solve our model, obtaining an expression for the average search time of Cas9 for its target. We find that experimentally measured kinetic parameters are close to the values yielding an optimal search time. Our results rationalize the role of PAMs in guiding the search process, and show that Cas9 searches for its targets in a nearly optimal way.