Restraining the V(D)J recombinase.
Chromosome breakage--a dangerous event that has triggered the evolution of several double-strand break repair pathways--has been co-opted by the immune system as an integral part of B- and T-cell development. This is a daring strategy, as improper repair can be deadly for the cell, if not for the whole organism. Even more daring, however, is the choice of a promiscuous transposase as the nuclease responsible for chromosome breakage, as the possibility of transposition brings an entirely new set of risks. What mechanisms constrain the dangerous potential of the recombinase and preserve genomic integrity during immune-system development?
Roth
David B
DB
Department of Pathology, Program in Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York 10016, USA. roth@saturn.med.nyu.edu
D000818:Animals; D019457:Chromosome Breakage / Q000235:genetics / Q000276:immunology*; D004249:DNA Damage / Q000235:genetics / Q000276:immunology; D004254:DNA Nucleotidyltransferases / Q000235:genetics / Q000276:immunology*; D004260:DNA Repair / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D009687:Nuclear Proteins; D011995:Recombination, Genetic / Q000235:genetics / Q000276:immunology*; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases