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.DOI: http://dx.doi.org/10.7554/eLife.03110.001.
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| http://dx.doi.org/10.7554/eLife.03110 | DOI Listing |
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Article Synopsis
- Sir2 is a histone deacetylase that helps maintain the stability of ribosomal RNA genes in budding yeast by preventing DNA breaks from leading to changes in rDNA copy number.
- It does this by suppressing transcription near issues that arise during DNA replication, which can otherwise provoke double-strand breaks (DSBs) and subsequent DNA repair processes.
- When Sir2 is absent, increased transcription can lead to DSBs, resulting in unstable rDNA copy numbers and the formation of extrachromosomal DNA, highlighting the importance of Sir2 in maintaining rDNA integrity.
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