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Series GSE106922 Query DataSets for GSE106922
Status Public on Jan 08, 2018
Title DNA Double-strand Break Response Factors Influence End-joining Features of IgH Class Switch and General Translocation junctions
Organism Mus musculus
Experiment type Other
Summary IgH class switch recombination (CSR) in B lymphocytes switches IgH constant regions to change antibody functions. CSR is initiated by DNA double strand breaks (DSBs) within a donor IgH switch (S) region and a downstream acceptor S region. CSR is completed by fusing donor and acceptor S region DSB ends by classical non-homologous end-joining (C-NHEJ) and, in its absence, by alternative end-joining (A-EJ) that is more biased to use longer junctional micro-homologies (MHs). Deficiency for DSB response (DSBR) factors, including ATM and 53BP1, variably impair CSR end-joining, with 53BP1 deficiency having the greatest impact. However, studies of potential impact of DSBR factor deficiencies on MH-mediated CSR end-joining have been technically limited. We now use a robust DSB joining assay to elucidate impacts of deficiencies for DSBR factors on CSR and chromosomal translocation junctions in primary mouse B cells and CH12F3 B lymphoma cells. Compared to wild-type, CSR and c-Myc to S region translocation junctions in the absence of 53BP1, and to a lesser extent other DSBR factors, have increased MH-utilization; indeed, 53BP1-deficient MH-profiles resemble those associated with C-NHEJ deficiency. Yet, translocation junctions between c-Myc DSB and general DSBs genome-wide are not MH-biased in ATM-deficient versus wild-type CH12F3 cells and less biased in 53BP1- and C-NHEJ-deficient cells than CSR junctions or c-Myc to S region translocation junctions. We discuss potential roles of DSBR factors in suppressing increased MH-mediated DSB end-joining and features of S regions that may render their DSBs prone to MH-biased end-joining in the absence of DSBR factors.
Overall design We performed HTGTS with different B cells and CH12F3 cells genotypes which utilizes AID-initiated 5'Smu DSBs as bait to study their junction features to other AID-initiated S region breaks. We also examine junction features of Cas9-induced c-myc locus DSB translocations to general genome-wide DSBs and S region DSBs.
Contributor(s) Panchakshari RA, Zhang X, Dong J, Alt FW
Citation(s) 29311308
Submission date Nov 15, 2017
Last update date May 15, 2019
Contact name Rohit A Panchakshari
Organization name Children's Hospital Boston
Department PCMM
Lab Frederick W. Alt Lab
Street address One Blackfan Circle, KARP building
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (48)
GSM2857653 WT-NCDel #1_5'Sm_rep1
GSM2857654 WT-NCDel #1_5'Sm_rep2
GSM2857655 WT-NCDel #1_5'Sm_rep3
BioProject PRJNA418463
SRA SRP125036

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Supplementary file Size Download File type/resource
GSE106922_RAW.tar 55.8 Mb (http)(custom) TAR (of XLS)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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