New concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2.
The lymphoid-specific factors, recombination-activating gene 1 (RAG1) and RAG2, initiate V(D)J recombination by introducing DNA double-stand breaks at specific sites in the genome. In addition to this critical endonuclease activity, the RAG proteins catalyze other chemical reactions that can affect the outcome of V(D)J recombination, one of which is transposition. While the transposition activity of the RAG proteins is thought to have been critical for the evolution of modern antigen-receptor loci, it has also been proposed to contribute to chromosomal translocations and lymphoid malignancy. A major challenge has been to determine how the transposition activity of the RAG proteins is regulated in vivo. Although a variety of mechanisms have been suggested by recent studies, a clear resolution of this issue remains elusive.
Chatterji
Monalisa
M
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Tsai
Chia-Lun
CL
Schatz
David G
DG
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D011995:Recombination, Genetic; D014178:Translocation, Genetic; D019895:Transposases / Q000276:immunology / Q000502:physiology*; D045567:VDJ Recombinases / Q000276:immunology / Q000378:metabolism
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D019895:Transposases; D045567:VDJ Recombinases