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| Status |
Public on Jan 01, 2020 |
| Title |
Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [END-seq] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
During V(D)J recombination RAG proteins introduce DNA double strand breaks (DSBs) adjacent to conserved recombination signal sequences (RSS) that contain either 12- or 23-nucleotide spacer regions. Coordinated cleavage following the “12/23” rule predicts that DSBs at variable (V) gene segments should not exceed the level of breakage at joining (J) segments, thereby ensuring that V regions do not engage in undesirable recombination events with one another. Here we report abundant RAG dependent DSBs at a multitude of V gene segments within the Ig locus independent of V-J rearrangement. We discover that a large fraction of V gene segments are flanked not only by a bone-fide 12 spacer, but also an overlapping, 23 spacer flipped RSS. These compatible pairs of RSS mediate recombination and deletion inside the V cluster even in the complete absence of J gene segments, and support a novel recombination center (RC) independent of the conventional J-centered RC. We propose a model that explains V gene segment usage by taking into account not only the probability of V-to-J rearrangement but also the surprisingly frequent, evolutionarily conserved intra-V cluster recombination events. These findings shed light on the diverse molecular strategies that shape the primary antigen receptor repertoires.
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| Overall design |
END-seq profile in abelson-transformed pre-B cells, primary bone marrow pre-B cells, and thymocytes.
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| Contributor(s) |
Shindoa K, Maman Y, Canela A, Shchatz DG, Livak F, Nussenzweig A |
| Citation(s) |
31875554 |
| |
| Submission date |
Nov 18, 2019 |
| Last update date |
Jul 02, 2021 |
| Contact name |
Yaakov Maman |
| Organization name |
Bar-Ilan University
|
| Department |
Azrieli Faculty of Medicine
|
| Lab |
Genome Instability & Cancer
|
| Street address |
Henrietta Szold 8
|
| City |
Safed |
| ZIP/Postal code |
1311502 |
| Country |
Israel |
| |
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| Platforms (1) |
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| Samples (19)
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| This SubSeries is part of SuperSeries: |
| GSE140677 |
Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire |
|
| Relations |
| BioProject |
PRJNA590463 |
| SRA |
SRP230614 |
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