Role of the translocation partner in protection against AID-dependent chromosomal translocations.

摘要: Chromosome translocations between Ig (Ig) and non-Ig genes are frequently associated with B-cell lymphomas in humans mice. The best characterized of these is c-myc/IgH translocation, which Burkitt’s lymphoma. These caused by activation-induced cytidine deaminase (AID), produces double-strand DNA breaks both genes. rare events, part because ATM, p53, p19 actively suppress them. To further define the mechanism protection against accumulation cells that bear we assayed B from mice carry mutations cell-cycle apoptosis regulator proteins act downstream p53. We find PUMA, Bim, PKCδ required for whereas Bcl-XL BAFF enhance translocation. Whether effects general or specific to translocation whether AID dsDNA other than c-myc not known. examine questions, developed an assay IgH Igβ, somatically mutated AID. Igβ/IgH, like translocations, AID-dependent, responsible lesions on non-IgH partners. However, do protect Igβ/IgH translocations. Instead, protected a BAFF- PKCδ-dependent pathway. conclude AID-induced lead their at least two nonoverlapping pathways primary cells.