GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE39108 Query DataSets for GSE39108
Status Public on Jul 05, 2012
Title UNG shapes the specifity of AID-induced somatic hypermutation in non 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 non B cells. NIH-3T3 cells were co-transduced with mOrangeSTOP and AID-ER–expressing vectors, together with Ugi (UNG inhibitor), UNG, or empty vector as control (n=3). Transduced cells were cultured in the presence of OHT during 11 d. AID-E58Q-ER vector (catalytically inactive form of AID) was used as a negative control in combination with the previously described constructions (n=3).
Contributor(s) Pérez-Durán P, Belver L, de Yébenes VG, Delgado P, Pisano DG, Ramiro AR
Citation(s) 22665573
Submission date Jul 04, 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 (18)
GSM956216 Exp1 Control AID
GSM956217 Exp1 Ugi AID
GSM956218 Exp1 UNG AID
This SubSeries is part of SuperSeries:
GSE39115 UNG shapes the specificity of AID-induced somatic hypermutation
BioProject PRJNA170048
SRA SRP014022

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE39108_SuppTableI.xlsx.gz 1.5 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Processed data are available on Series record
Raw data are available in SRA

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap