DNA topology and V(D)J recombination: a tentative connection.

Gene recombination is the fundamental basis of immunoglobulin (Ig) and T cell receptor (TCR) diversity. Although several specific and nonspecific enzymatic equipments were revealed to be necessary for Ig and TcR gene assembly, almost nothing is known about the developmental and tissue specific control of recombination and the individual functions of the heptameric and nonameric signals and 12/23 spacers in this process. According to certain conformational and functional respects, we consider the nonamer a DNA insertion site to the nuclear scaffold, in relation with its structural homology to the satellite (5'-ACAAACC-3') and microsatellite repetitions, involved in DNA-nucleoskeleton impact. A topological control for V(D)J recombination is proposed, through different accessibilities of the substrates in the catalytic site, defined by a specific nonamer-mediated insertion to the nuclear scaffold. Recognition of heptamer and nonamer sequences by RAG proteins is followed by the assembly of an asymmetric recombinant complex. Even more important in this assembly may be the role of nonamer which, through DNA flexibilization and bending, could participate at the formation of the enzyme core. This core with the attached DNA could have a nucleosome-like geometry, a motif present in certain DNA processing enzymatic systems. Such an assumption emerges from the close homology of the nonamers with the DNA mobilization intergenic sequences (CA5-6T), found in many eukaryotic organisms.