Transcriptional stalling in B-lymphocytes

Department of Microbiology and Immunology
Transcription 04/2013; 4(3). DOI: 10.4161/trns.24556
Source: PubMed


B cells utilize three DNA alteration strategies-V(D)J recombination, somatic hypermutation (SHM) and class switch recombination (CSR)-to somatically mutate their genome, thereby expressing a plethora of antibodies tailor-made against the innumerable antigens they encounter while in circulation. Of these three events, the single-strand DNA cytidine deaminase, Activation Induced cytidine Deaminase (AID), is responsible for SHM and CSR. Recent advances, discussed in this review article, point toward various components of RNA polymerase II "stalling" machinery as regulators of AID activity during antibody diversification and maintenance of B cell genome integrity.

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Available from: Jianbo Sun, Jul 17, 2014
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    • "Stalled RNA pol II complexes occur during encounter with various obstacles caused by (a) the presence of antisense transcription, (b) secondary DNA structures including those caused by G-richness on the non-template strand of S sequences, (c) variation in the levels of elongation promoting chromatin modifications, and (d) the presence of mutations or DNA lesions on the template DNA (4, 39, 40). Resolution of the stalled complex includes mechanisms of backtracking or early termination of the complex, which dissociates the RNA from RNA pol II (41), or ubiquitin-mediated destabilization of RNA pol II (42, 48). These mechanisms reveal a free 3′-end RNA substrate for RNA exosome, a co-factor of AID. "
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