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Series GSE39114 Query DataSets for GSE39114
Status Public on Jul 05, 2012
Title UNG shapes the specifity of AID-induced somatic hypermutation in B cells
Organism Mus musculus
Experiment type Other
Summary Secondary diversification of antibodies through somatic hypermutation (SHM) and class switch recombination (CSR) is a critical component of the immune response. Activation-induced deaminase (AID) initiates both processes by deaminating cytosine residues in immunoglobulin genes. The resulting U:G mismatch can be processed by alternative pathways to give rise to a mutation (SHM) or a DNA double-strand break (CSR). Central to this processing is the activity of uracil-N-glycosylase (UNG), an enzyme normally involved in error-free base excision repair. We used next generation sequencing to analyze the contribution of UNG to the resolution of AID-induced lesions. Loss- and gain-of-function experiments showed that UNG activity can promote both error-prone and high fidelity repair of U:G lesions. Unexpectedly, the balance between these alternative outcomes was influenced by the sequence context of the deaminated cytosine, with individual hotspots exhibiting higher susceptibility to UNG-triggered error-free or error-prone resolution. These results reveal UNG as a new molecular layer that shapes the specificity of AID-induced mutations and may provide new insights into the role of AID in cancer development.
Overall design Next Generation Sequencing analysis of mutations introduced by AID in activated B lymphocytes from WT and UNG-/- mice (n=4). Activated B cells from AID-/- mice (n=2) were used as negative controls.
Contributor(s) Pérez-Durán P, Ramiro AR
Citation(s) 22665573
Submission date Jul 05, 2012
Last update date May 15, 2019
Contact name Pablo Perez-Duran
Organization name Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Street address Melchor Fernandez Almagro, 3
City Madrid
ZIP/Postal code 28002
Country Spain
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (10)
GSM956309 UNG+/+ 1
GSM956310 UNG+/+ 2
GSM956311 UNG+/+ 3
This SubSeries is part of SuperSeries:
GSE39115 UNG shapes the specificity of AID-induced somatic hypermutation
BioProject PRJNA170049
SRA SRP014024

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Supplementary file Size Download File type/resource
GSE39114_SuppTableII.xlsx.gz 745.4 Kb (ftp)(http) XLSX
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Processed data are available on Series record
Raw data are available in SRA

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