text: thumb|right|450px|Fig. 2. Ser-Recombinases: The (essentially irreversible) subunit-rotation pathway.<br /><br />Contrary to Tyr-recombinases, the four participating DNA strands are cut in synchrony at points staggered by only 2 bp (leaving little room for proofreading). Subunit-rotation (180°) permits the exchange of strands while covalently linked to the protein partner. The intermediate exposure of double-strand breaks bears risks of triggering illegitimate recombination and thereby secondary reactions.<br /><br />Here, the synaptic complex arises from the association of pre-formed recombinase dimers with the respective target sites (CTD/NTD, C-/N-terminal domain). Like for Tyr-recombinases, each site contains two arms, each accommodating one protomer. As both arms are structured slightly differently, the subunits become conformationally tuned and thereby prepared for their respective role in the  recombination cycle. Contrary to members of the Tyr-class the recombination pathway converts two different substrate sites (attP and attB) to site-hybrids [[site-specific recombinase technology|(attL and attR). This explains the irreversible nature of this particular recombination pathway, which can only be overcome by auxiliary "recombination directionality factors" (RDFs).]]
  Based on amino acid sequence homologies and mechanistic relatedness, most site-specific recombinases are grouped into one of two families: the tyrosine (Tyr) recombinase family or serine (Ser) recombinase family. The names stem from the conserved nucleophilic amino acid residue present in each class of recombinase which is used to attack the DNA and which becomes covalently linked to it during strand exchange. The earliest identified members of the serine recombinase family were known as resolvases or DNA invertases, while the founding member of the tyrosine recombinases, lambda phage integrase (using attP/B recognition sites), differs from the now well-known enzymes such as Cre (from the P1 phage) and FLP (from the yeast Saccharomyces cerevisiae). Famous serine recombinases include enzymes such as gamma-delta resolvase (from the Tn1000 transposon), Tn3 resolvase (from the Tn3 transposon), and φC31 integrase (from the φC31 phage).
  Although the individual members of the two recombinase families can perform reactions with the same practical outcomes, the families are unrelated to each other, having different protein structures and reaction mechanisms. Unlike tyrosine recombinases, serine recombinases are highly modular, as was first hinted by biochemical studies and later shown by crystallographic structures. Knowledge of these protein structures could prove useful when attempting to re-engineer recombinase proteins as tools for genetic manipulation.