Protein and DNA Conformational Changes Contribute to Specificity of Cre Recombinase.

ABSTRACT: Cre, a conservative site-specific tyrosine recombinase, is a powerful gene editing tool in the laboratory. Expanded applications in human health are hindered by a lack of understanding of the mechanism by which Cre selectively binds and recombines its cognate loxP sequences. This knowledge is essential for retargeting the enzyme to new sites and for mitigating the effects of off-target recombination. Prior studies have suggested that in addition to a few base-specific contacts to cognate loxP DNA, the enzyme's specificity is enhanced by (1) autoinhibition involving a conformational change in the protein's C-terminal helix and (2) indirect readout via binding-coupled conformational changes in the target DNA. We used isothermal titration calorimetry (ITC), circular dichroism (C

SUBMITTER: Montgomery JS 

PROVIDER: S-EPMC12707689 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature