Researchers reported in a preprint that Cre recombinase tucks part of its DNA-binding surface away while searching DNA. This promotes movement along DNA and limits unwanted binding. Recognizing a matching loxP sequence lifts the restraint, allowing stable binding and assembly of the recombination complex.
The study reveals a specific control switch: Cre weakens unwanted DNA contacts while it scans, then binds firmly when it finds the right sequence. This mechanism may guide the design of DNA-modifying enzymes that must search large genomes efficiently while limiting off-target complex formation.
✦ Cre searches DNA efficiently by briefly keeping its binding surface restrained.