title: V(D)J recombination: mechanisms of initiation.
abstract: V(D)J recombination assembles immunoglobulin and T cell receptor genes during lymphocyte development through a series of carefully orchestrated DNA breakage and rejoining events. DNA cleavage requires a series of protein-DNA complexes containing the RAG1 and RAG2 proteins and recombination signals that flank the recombining gene segments. In this review, we discuss recent advances in our understanding of the function and domain organization of the RAG proteins, the composition and structure of RAG-DNA complexes, and the pathways that lead to the formation of these complexes. We also consider the functional significance of RAG-mediated histone recognition and ubiquitin ligase activities, and the role played by RAG in ensuring proper repair of DNA breaks made during V(D)J recombination. Finally, we propose a model for the formation of RAG-DNA complexes that involves anchoring of RAG1 at the recombination signal nonamer and RAG2-dependent surveillance of adjoining DNA for suitable spacer and heptamer sequences.
authors.affiliation: Department of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA. david.schatz@yale.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Schatz
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Swanson
mesh_terms: D000818:Animals; D053837:DNA Cleavage; D053938:DNA Fragmentation; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000302:isolation & purification; D024002:HMGB Proteins / Q000737:chemistry; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000302:isolation & purification; D051379:Mice; D046912:Multiprotein Complexes / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry; D054875:Ubiquitination; D060152:V(D)J Recombination
chemical_list: D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; C499308:Rag2 protein, mouse; C064658:RAG-1 protein; D044767:Ubiquitin-Protein Ligases