2014
DOI: 10.1016/j.cell.2014.11.014
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Convergent Transcription at Intragenic Super-Enhancers Targets AID-Initiated Genomic Instability

Abstract: Summary Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) for antibody affinity maturation and DNA breakage for antibody class switch recombination (CSR) via transcription-dependent cytidine deamination of single stranded DNA targets. While largely specific for immunoglobulin genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. How AID is recruited to off-targets has been a long-standing … Show more

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Cited by 222 publications
(268 citation statements)
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References 69 publications
(135 reference statements)
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“…Aggregate patterns of transcription profiles showed enrichment of reads within 1.5 kb of TSSs genome-wide (Fig. S1B, Right), consistent with previously published GRO-seq results obtained in other cell types (30,31). To perform HTGTS for DSB identification, we used a Cas9:sgRNAbased approach to introduce HTGTS bait DSBs into primary NSPCs isolated from Xrcc4 −/− p53 −/− mice, as previously described (4).…”
Section: Dsbs and Translocations Are Enriched Around Active Tsss In Nsupporting
confidence: 57%
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“…Aggregate patterns of transcription profiles showed enrichment of reads within 1.5 kb of TSSs genome-wide (Fig. S1B, Right), consistent with previously published GRO-seq results obtained in other cell types (30,31). To perform HTGTS for DSB identification, we used a Cas9:sgRNAbased approach to introduce HTGTS bait DSBs into primary NSPCs isolated from Xrcc4 −/− p53 −/− mice, as previously described (4).…”
Section: Dsbs and Translocations Are Enriched Around Active Tsss In Nsupporting
confidence: 57%
“…To investigate further the set of transcribed genes that contained TSS-proximal junctions in NSPCs, we performed a comparative analysis of GRO-seq transcription profiles of NSPCs and those previously generated for activated B cells (31). This analysis yielded sets of genes transcribed in NSPCs but not in B cells (class 1), genes commonly transcribed in both NSPCs and B cells (class 2), and genes transcribed in B cells but not in NSPCs (class 3).…”
Section: Dsbs and Translocations Are Enriched Around Active Tsss In Nmentioning
confidence: 99%
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“…LAM-HTGTS, like its predecessor HTGTS (17), employs a single primer for a DSB-associated bait sequence to perform linear amplification across bait-prey junctions to identify all prey sequences joined to the bait DSBs in an unbiased manner (16,18). We have used various types of DSBs as bait for LAM-HTGTS, including those generated by engineered nucleases and endogenous DSBs (17)(18)(19)(20)(21)(22). Because V(D)J recombination generates rearrangements with junctions at borders of V, D, and J segments, we can use primers for any of these gene segments as LAM-HTGTS bait to identify sites of RAG-generated DSBs, both in progenitor or precursor lymphocytes undergoing V(D)J recombination, as well as in mature lymphocytes to retrospectively identify V(D)J recombination events that occurred earlier in development.…”
Section: Significancementioning
confidence: 99%