RAGI and RAG2 are the key components of the V(D)J recombinase machinery tha
t catalyses the somatic gene rearrangements of antigen receptor genes durin
g lymphocyte development. In the first step of V(D)J recombination - DNA cl
eavage - the RAG proteins act together as an endonuclease to excise the DNA
between two individual gene segments. They are also thought to be involved
in the subsequent DNA joining step. In vitro, the RAG proteins catalyze th
e integration of the excised DNA element into target DNA completing a proce
ss similar to bacterial transposition. In vivo, this reaction is suppressed
by an unknown mechanism. The individual roles of RAG1 and RAG2 in V(D)J re
combination and transposition reactions are discussed based on mutation ana
lyses and structure predictions.