It is a curious fact that two unrelated families of enzymes have evolved that promote conservative site-specific recombination. Elsewhere in this volume (see Chapter 2), a large family of “tyrosine recombinases” is described, of which phage lambda integrase is the most famous and senior member. The subject of this chapter is a second large family, the “serine recombinases.” The names come from the conserved residue of the recombinase that provides the nucleophile to attack and break the DNA phosphodiester backbone (see “Tn3 and γδ resolvases: cointegrate resolution” section). Although the serine and tyrosine recombinases are unrelated in sequence, structure, or mechanism, there is no obvious distinction between their biological functions. Why two very different types of site-specific recombinases have survived eons of natural selection, yet continue to play similar roles, remains a mystery. Serine recombinases are widespread in the Eubacteria and Archea, but not in Eukarya, where the few examples found so far may be of recent bacterial origin.

A serine recombinase can be identified by similarity of parts or all of its primary amino acid sequence to that of one of the archetypal members of the family [e.g. Tn3 resolvase (Fig. 3.7)]. Several hundreds of such proteins can now be predicted from available DNA sequences (reviewed by Smith and Thorpe, 2002). The relations of the members of the family are discussed later in this chapter.