The ins and outs of serine integrase site-specific recombination

Serine integrases catalyze the integration and excision of phage genomes into and out of bacterial chromosomes in a highly specific and directional manner, making these proteins powerful tools for genome engineering. In 2013, the first structure of a serine integrase-DNA complex was reported. This work revealed how the phage attP sequence is recognized by the integrase and provided important clues about how serine integrases bind to other attachment site sequences. The resulting structural models indicate that distinct spatial arrangements of integrase domains are present for each attachment site complex. Here we describe how serine integrases may exploit this site-dependent domain arrangement to regulate the direction of recombination. We also discuss how phage-encoded recombination directionality factors could change this directionality by altering the nature of inter-subunit interactions.