Figure 2.

Mechanism of the V(D)J recombination. (a). Recombination Signal Sequence (RSS). In 12RSS (represented by open triangle), the heptamer is separated from nonamer by 12 bp and in 23RSS (represented by closed triangle) by 23 bp. (b). Distribution of RSS at the seven antigen receptor loci in human beings and the 12/23 rule. The V, D and J regions of the coding segments are depicted as rectangles; the flanking 12RSS is represented by an open triangle and 23RSS by a closed triangle. As per the ‘12/23 rule’, V(D)J recombination is restricted to gene segments that are flanked by signals of different spacer lengths. (c). Mechanism of V(D)J recombination. Schematic model of the protein–DNA complexes in V(D)J recombination. The 12RSS and 23RSS are represented as white and blue triangles, respectively. Coding segments are shown as rectangles and proteins as shaded ovals. ‘V’ stands for variable and ‘J’ for joining gene segments. Recombination activating genes (RAGs; shaded ovals) bind the RSS and introduce a single-strand nick in the DNA precisely at the border between the heptamer of RSS and the coding segment. This nick generates a free 3′-OH group on the coding end which is then covalently linked to the opposing phosphodiester bond, leaving a covalently closed hairpin on the coding end and a blunt 5′ phosphorylated signal end. The ends remain associated with RAGs; constituting a transitory structure referred to as ‘post-cleavage complex’. Following this, the coding ends are processed and joined by NHEJ to create the exon, which forms the antigen-binding region of antigen receptors. Signal end remains bound to RAGs constituting a ‘signal end complex’ that forms the signal joint.