Immunoglobulin Class Switch Recombination Is Initiated by Rare Cytosine Deamination Events at Switch Regions
Copyright © 2020 American Society for Microbiology..
Activation-induced cytidine deaminase (AID) initiates immunoglobulin (Ig) class switch recombination (CSR), somatic hypermutation (SHM), and gene conversion by converting DNA cytosines to uracils at specific genomic regions. In this study, we examined AID footprints across the entire length of an engineered switch region in cells ablated for uracil repair. We found that AID deamination occurs predominantly at WRC hot spots (where W is A or T and R is A or G) and that the deamination frequency remains constant across the entire switch region. Importantly, we analyzed monoallelic AID deamination footprints on both DNA strands occurring within a single cell cycle. We found that AID generates few and mostly isolated uracils in the switch region, although processive AID deaminations are evident in some molecules. The frequency of molecules containing deamination on both DNA strands at the acceptor switch region correlates with the class switch efficiency, raising the possibility that the minimal requirement for DNA double-strand break (DSB) formation is as low as even one AID deamination event on both DNA strands.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Molecular and cellular biology - 40(2020), 16 vom: 29. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Ahrom [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.08.2020 Date Revised 30.01.2021 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.1128/MCB.00125-20 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310932777 |
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| 500 | |a Date Revised 30.01.2021 | ||
| 500 | |a published: Electronic-Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 American Society for Microbiology. | ||
| 520 | |a Activation-induced cytidine deaminase (AID) initiates immunoglobulin (Ig) class switch recombination (CSR), somatic hypermutation (SHM), and gene conversion by converting DNA cytosines to uracils at specific genomic regions. In this study, we examined AID footprints across the entire length of an engineered switch region in cells ablated for uracil repair. We found that AID deamination occurs predominantly at WRC hot spots (where W is A or T and R is A or G) and that the deamination frequency remains constant across the entire switch region. Importantly, we analyzed monoallelic AID deamination footprints on both DNA strands occurring within a single cell cycle. We found that AID generates few and mostly isolated uracils in the switch region, although processive AID deaminations are evident in some molecules. The frequency of molecules containing deamination on both DNA strands at the acceptor switch region correlates with the class switch efficiency, raising the possibility that the minimal requirement for DNA double-strand break (DSB) formation is as low as even one AID deamination event on both DNA strands | ||
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| 650 | 4 | |a activation-induced cytidine deaminase | |
| 650 | 4 | |a base excision | |
| 650 | 4 | |a class switch recombination | |
| 650 | 4 | |a mismatch repair | |
| 650 | 4 | |a somatic hypermutation | |
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