Regulation of RAG transposition.
V(D)J recombination is initiated by the lymphoid specific proteins RAG1 and RAG2, which together constitute the V(D)J recombinase. However, the RAG 1/2 complex can also act as a transposase, inserting the broken DNA molecules generated during V(D)J recombination into an unrelated piece of DNA. This process, termed RAG transposition, can potentially cause insertional mutagenesis, chromosomal translocations and genomic instability. This review focuses on the mechanism and regulation of RAG transposition. We first provide a brief overview of the biochemistry of V(D)J recombination. We then discuss the discovery of RAG transposition and present an overview of the RAG transposition pathway. Using this pathway as a framework, we discuss the factors and forces that regulate RAG transposition.
Matthews
Adam G W
AG
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. agwmatthews@gmail.com
Oettinger
Marjorie A
MA
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D016654:Genes, RAG-1; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D016254:Mutagenesis, Insertional; D011995:Recombination, Genetic; D014178:Translocation, Genetic; D045567:VDJ Recombinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D045567:VDJ Recombinases