Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs.
RAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end-joining (NHEJ) proteins then join the coding segments and join the RSs. In wild-type cells, both full-length and truncated ("core") RAGs lead to accumulation of "hybrid" V(D)J joins, in which an RS is appended to a different coding sequence. We now show that while hybrid joins do not accumulate in NHEJ-deficient cells that express full-length RAGs, they do accumulate in NHEJ-deficient cells that express the core RAGS; like those catalyzed by core RAGs in vitro, however, they are sealed on just one DNA strand. These results suggest a potential role for the non-core regions in repressing potentially harmful transposition events.
Sekiguchi
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JA
Howard Hughes Medical Institute, Harvard University Medical School, Boston, MA 02115, USA.
Whitlow
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D000818:Animals; D034961:Antigens, Nuclear; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000172:deficiency / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D016654:Genes, RAG-1 / Q000235:genetics; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000072200:Ku Autoantigen; D051379:Mice; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C101467:XRCC4 protein, human; C064658:RAG-1 protein; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen; D011088:DNA Ligases; D000072481:DNA Ligase ATP