Figure 8.

Schematic diagrams depicting models for short-range collision– and long-range scanning–mediated D-to-J recombination. (A) Schematic of murine Igh depicting some D_H and J_H gene segments. Gray box represents the RC, encompassing J_H gene segments and DQ52. Gene segments are depicted as rectangles, 23RSSs as gray triangles, and 3′ and 5′ D_H 12RSSs as orange and purple triangles, respectively. (B) Long-range recombination is thought to occur through RAG chromatin scanning in which the cohesin ring brings RSSs into the RC in close proximity of RSS-bound RAG in a topologically constrained manner. Panel i: DQ52, which resides very close to the J_H gene segments, has already been extruded through the cohesin ring and now is separated from J_H by cohesin. Long-range recombination (panels ii and iii) occurs predominantly by deletion due to the topological constraint imposed by cohesin. (C) Short-range recombination occurs through collision-mediated recombination, largely topologically unconstrained. Short-range recombination can result in either inversion or deletion; however, DQ52-to-J_H recombination occurs almost exclusively by deletion due to the different sequences of its 5′ and 3′ RSSs (Zhang et al., 2019). Models in B and C adapted from Zhang et al. (2019). This figure was created with BioRender.com.