title: Antigen receptor diversification and chromosome translocations.
abstract: Double-stranded DNA breaks (DSBs) can result in chromosomal abnormalities, including deletions, translocations and aneuploidy, which can promote neoplastic transformation. DSBs arise accidentally during DNA replication and can be induced by environmental factors such as ultraviolet light or ionizing radiation, and they are generated during antigen receptor-diversification reactions in lymphocytes. Cellular pathways that maintain genomic integrity use sophisticated mechanisms that recognize and repair all DSBs regardless of their origin. Such pathways, along with DNA-damage checkpoints, ensure that either the damage is properly repaired or cells with damaged DNA are eliminated. Here we review how impaired DNA-repair or DNA-damage checkpoints can lead to genetic instability and predispose lymphocytes undergoing diversification of antigen receptor genes to malignant transformation.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021-6399, USA.
authors.forename: Mila
authors.initials: M
authors.lastname: Jankovic
authors.forename: André
authors.initials: A
authors.lastname: Nussenzweig
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D000916:Antibody Diversity / Q000235:genetics* / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology*; D011946:Receptors, Antigen / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics* / Q000276:immunology
chemical_list: D011946:Receptors, Antigen