STIMULATION OF V(D)J CLEAVAGE BY HIGH-MOBILITY GROUP PROTEINS

V(D)J recombination requires a pair of signal sequences with spacer le ngths of 12 and 23 bp between the conserved heptamer and nonamer eleme nts. The RAG1 and RAG2 proteins initiate the reaction by making double -strand DNA breaks at both signals, and must thus be able to operate o n these two different spatial arrangements. We show that the DNA-bendi ng proteins HMG1 and HMG2 stimulate cleavage and RAG protein binding a t the 23 bp spacer signal. These findings suggest that DNA bending is important for bridging the longer spacer, and explain how a similar ar ray of RAG proteins could accommodate a signal with either a 12 or a 2 3 bp spacer. An additional effect of HMG proteins is to stimulate coup led cleavage greatly when both signal sequences are present, suggestin g that these proteins also aid the formation of a synaptic complex.