title: Mechanisms of programmed DNA lesions and genomic instability in the immune system.
abstract: Chromosomal translocations involving antigen receptor loci are common in lymphoid malignancies. Translocations require DNA double-strand breaks (DSBs) at two chromosomal sites, their physical juxtaposition, and their fusion by end-joining. Ability of lymphocytes to generate diverse repertoires of antigen receptors and effector antibodies derives from programmed genomic alterations that produce DSBs. We discuss these lymphocyte-specific processes, with a focus on mechanisms that provide requisite DSB target specificity and mechanisms that suppress DSB translocation. We also discuss recent work that provides new insights into DSB repair pathways and the influences of three-dimensional genome organization on physiological processes and cancer genomes.
authors: Departments of Genetics and Pediatrics, Harvard Medical School, Boston, MA 02115, USA. alt@enders.tch.harvard.edu
authors: Frederick W
authors: FW
authors: Alt
authors: Yu
authors: Y
authors: Zhang
authors: Fei-Long
authors: FL
authors: Meng
authors: Chunguang
authors: C
authors: Guo
authors: Bjoern
authors: B
authors: Schwer
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008223:Lymphoma / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014178:Translocation, Genetic; D060152:V(D)J Recombination
chemical_list: D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell
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