Class Switch Recombination: An Emerging Mechanism
Class switch recombination (CSR) has been the least well understood of the Ig gene DNA rearrangements. The discovery that activation-induced deaminase (AID) is a pivotal player in CSR as well as somatic hypermutation (SHM) and its variant, gene conversion, represents a sea change in our understanding of these processes. The recognition that AID directly deaminates ssDNA has provided a springboard toward the emergence of a model that explains the initiation of these events. Nonhomologous end joining (NHEJ), the main pathway for the repair of double-strand breaks in mammalian cells plays a key role in the resolution of CSR transactions. Mediators of general double-strand break repair are also involved in CSR and are mutated in several immunodeficiency diseases. A global picture of the mechanism of CSR is emerging and is providing new insights toward understanding the genetic events that underlie B cell cancers.
KeywordsBase Excision Repair Primary Immunodeficiency Disease Class Switch Recombination Nijmegen Breakage Syndrome Histone Hyperacetylation
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- Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, Reina-San-Martin B, Coppola V, Meffre E, Difilippantonio MJ, Redon C, Pilch DR, Olaru A, Eckhaus M, Camerini-Otero RD, Tessarollo L, Livak F, Manova K, Bonner WM, Nussenzweig MC, Nussenzweig A (2002) Science 296:922–927PubMedGoogle Scholar
- Du J, Zu Y, Shanmugam A, Kenter AL (1997) Nuc Acids Res 25:3066–3073Google Scholar
- Dunnick W, Hertz GZ, Scappino L, Gritzmacher C (1993) Nuc Acids Res 21:365–372Google Scholar
- Wegner R-D, Chrzanowska KH, Stumm M (1999) Ataxia-telangiectasia variants (Nijmegen breakage syndrome) In “Primary immunodeficiency diseases.” (Ochs HD, Smith CIE, Puck J.M (eds) Oxford University Press, New York, pp 324–334Google Scholar
- Whitmore C, Prowse DM, Haughton G, Arnold L (1991) Intl Immunol 3:95–103Google Scholar