VDJ Recombination Cell Volume 94, Issue 4, Pages 411-414 (August 1998) David B Roth, Nancy L Craig  Cell  Volume 94, Issue 4, Pages 411-414 (August 1998) DOI: 10.1016/S0092-8674(00)81580-9

Figure 1 Transposition and VDJ Recombination Global similarities between transposition and VDJ recombination are illustrated. (A) The RAG recombinase recognizes recombination signal sequences (triangles) adjacent to V, D, or J coding elements (rectangles). Double-strand breaks are introduced between the RSS and the coding elements, generating a pair of coding ends (left) and a pair of signal ends (right). Coding ends join, forming a coding joint. Signal ends join, forming a signal joint. Both joining reactions involve ligation mediated by cellular repair factors (see text). (B) The transposase recognizes specific sequences at the ends of the transposon (triangles) and introduces a double-strand break separating the element from the flanking sequences. Rejoining of the broken donor ends (left) by the cellular repair machinery yields a repaired donor site. The transposon ends join to a new target DNA molecule (dashed line) via transesterification, generating a simple insertion (see text). Cell 1998 94, 411-414DOI: (10.1016/S0092-8674(00)81580-9)

Figure 2 Transesterification Reactions Three RAG-mediated transesterification reactions are illustrated. (A) DSB formation proceeds by attack of the 3′ OH on a phosphodiester bond of the bottom strand, generating a hairpin coding end and a blunt signal end. (B) Hybrid joints are formed by attack of a 3′ OH of a signal end on a hairpin coding end. (C) Signal ends join to a target DNA molecule by transposition, a reaction involving attack of the 3′ OH groups on the phosphodiester bonds of the target DNA. Cell 1998 94, 411-414DOI: (10.1016/S0092-8674(00)81580-9)

Figure 3 RAG-Mediated Chromosome Translocations via Single End Insertions Single-ended transposition of a signal end to the target chromosome forms a branched intermediate, that can be further processed by RAG-mediated cleavage to yield a hairpin end and an RSS joined to the partner chromosome. Joining of the two hairpin ends forms the reciprocal translocation product. Cell 1998 94, 411-414DOI: (10.1016/S0092-8674(00)81580-9)

Figure 4 RAG-Mediated Chromosome Translocations via Double End Insertions Double-ended transposition of a pair of signal ends to the target chromosome generates a doubly nicked intermediate. RAG-mediated cleavage would excise the insert, leaving a pair of hairpin chromosome ends and an excised linear molecule with signal ends. Joining of the hairpin ends would produce a reciprocal translocation. The signal ends, which would be expected to carry short single-stranded extensions because of the staggered nature of target DNA cleavage (Hiom et al. 1998) might be joined to form a signal joint or could undergo further processing and perhaps additional transposition events. Cell 1998 94, 411-414DOI: (10.1016/S0092-8674(00)81580-9)