Multi-microsecond molecular dynamics unveils the mechanism of DNA traversal within CRISPR-Cas12a

Abstract

CRISPR-Cas12a is an emerging gene editing system that recently came to the forefront with innovative applications such as rapid and ultrasensitive nucleic acid detection. At the core of this molecular complex, the RNA-guided Cas12a enzyme cleaves its target double-stranded DNA using a single catalytic cleft in the RuvC domain. Despite extensive experimental research, it remains highly elusive how the DNA target strand is accommodated within the RuvC core for cleavage, making the “DNA traversal” a burgeoning question.