Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein
The activation induced cytidine deaminase (AID) protein is known to initiate somatic hypermutation, gene conversion or switch recombination by cytidine deamination within the immunoglobulin loci. Using chromosomally integrated fluorescence reporter transgenes, we demonstrate a new recombinogenic act...
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2014-07-01
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doaj-b98dd0701533462b8301536e36ba1e922021-05-04T23:13:28ZengeLife Sciences Publications LtdeLife2050-084X2014-07-01310.7554/eLife.03110Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) proteinJean-Marie Buerstedde0Noel Lowndes1David G Schatz2Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, IrelandCentre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, IrelandDepartment of Immunobiology, Yale University School of Medicine, New Haven, United States; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United StatesThe activation induced cytidine deaminase (AID) protein is known to initiate somatic hypermutation, gene conversion or switch recombination by cytidine deamination within the immunoglobulin loci. Using chromosomally integrated fluorescence reporter transgenes, we demonstrate a new recombinogenic activity of AID leading to intra- and intergenic deletions via homologous recombination of sequence repeats. Repeat recombination occurs at high frequencies even when the homologous sequences are hundreds of bases away from the positions of AID-mediated cytidine deamination, suggesting DNA end resection before strand invasion. Analysis of recombinants between homeologous repeats yielded evidence for heteroduplex formation and preferential migration of the Holliday junctions to the boundaries of sequence homology. These findings broaden the target and off-target mutagenic potential of AID and establish a novel system to study induced homologous recombination in vertebrate cells.https://elifesciences.org/articles/03110AIDhomologous recombinationDNA repair |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jean-Marie Buerstedde Noel Lowndes David G Schatz |
spellingShingle |
Jean-Marie Buerstedde Noel Lowndes David G Schatz Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein eLife AID homologous recombination DNA repair |
author_facet |
Jean-Marie Buerstedde Noel Lowndes David G Schatz |
author_sort |
Jean-Marie Buerstedde |
title |
Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein |
title_short |
Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein |
title_full |
Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein |
title_fullStr |
Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein |
title_full_unstemmed |
Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein |
title_sort |
induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (aid) protein |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2014-07-01 |
description |
The activation induced cytidine deaminase (AID) protein is known to initiate somatic hypermutation, gene conversion or switch recombination by cytidine deamination within the immunoglobulin loci. Using chromosomally integrated fluorescence reporter transgenes, we demonstrate a new recombinogenic activity of AID leading to intra- and intergenic deletions via homologous recombination of sequence repeats. Repeat recombination occurs at high frequencies even when the homologous sequences are hundreds of bases away from the positions of AID-mediated cytidine deamination, suggesting DNA end resection before strand invasion. Analysis of recombinants between homeologous repeats yielded evidence for heteroduplex formation and preferential migration of the Holliday junctions to the boundaries of sequence homology. These findings broaden the target and off-target mutagenic potential of AID and establish a novel system to study induced homologous recombination in vertebrate cells. |
topic |
AID homologous recombination DNA repair |
url |
https://elifesciences.org/articles/03110 |
work_keys_str_mv |
AT jeanmariebuerstedde inductionofhomologousrecombinationbetweensequencerepeatsbytheactivationinducedcytidinedeaminaseaidprotein AT noellowndes inductionofhomologousrecombinationbetweensequencerepeatsbytheactivationinducedcytidinedeaminaseaidprotein AT davidgschatz inductionofhomologousrecombinationbetweensequencerepeatsbytheactivationinducedcytidinedeaminaseaidprotein |
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1721477079184179200 |