Cre recombinase (Cre) (Cre)

Cre recombinase is a 38 kDa site-specific DNA recombinase belonging to the tyrosine recombinase family, originally derived from the P1 bacteriophage (UniProt: P06956) [1]. It is the central component of the Cre-loxP system, which facilitates precise DNA recombination between two 34-base pair recognition sequences known as loxP sites [2]. Depending on the orientation and location of these sites, Cre can induce DNA excision, inversion, or translocation, making it an indispensable tool for generating conditional knockout and knock-in genetic models [3]. The enzyme's activity can be temporally controlled using inducible systems, such as the Cre-ERT2 fusion protein that remains inactive in the cytoplasm until the administration of Tamoxifen or 4-hydroxytamoxifen [3]. Beyond its extensive use in basic research, Cre recombinase is being explored for therapeutic gene editing, including the potential to excise integrated viral genomes like HIV-1 or to correct deleterious mutations in genetic diseases [4]. However, its translation to the clinic is complicated by safety concerns such as off-target activity at pseudo-loxP sites in the human genome and the potential for an immune response against the non-human protein [5].

Other names

Cyclization recombination proteinP1 bacteriophage Cre recombinaseTyrosine-type site-specific recombinase Cre

Cre recombinase catalyzes site-specific DNA recombination between two 34-bp loxP sites. It utilizes a conserved tyrosine residue to perform a nucleophilic attack on the DNA phosphodiester backbone, creating a covalent protein-DNA intermediate. This process involves the formation of a Holliday junction and subsequent resolution to achieve DNA excision, inversion, or integration without the need for ATP or accessory proteins [1, 2].