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Series GSE84102 Query DataSets for GSE84102
Status Public on Aug 19, 2016
Title The PAXX and XLF DNA Repair Factors are Functionally Redundant in Joining DNA breaks in a G1-arrested Progenitor B Cell Line
Organism Mus musculus
Experiment type Other
Summary Classical non-homologous end-joining (C-NHEJ) is a major mammalian DNA double strand break (DSB) repair pathway. Core C-NHEJ factors, such as XRCC4, are required for joining DSB intermediates of the G1 phase-specific V(D)J recombination reaction in progenitor lymphocytes. Core factors also contribute to joining DSBs in cycling mature B-lineage cells, including DSBs generated during antibody class switch recombination (CSR) and DSBs generated by ionizing radiation (IR). The XLF C-NHEJ factor is dispensable for V(D)J recombination in normal cells, but, due to functional redundancy, is absolutely required for this process in cells deficient for the ATM DSB response factor. The recently identified PAralogue of XRCC4 and XLF (PAXX) factor has homology to these two proteins and variably contributes to IR-induced DSB repair in human and chicken cells. We now report that PAXX is dispensable for joining V(D)J recombination DSBs in G1-arrested mouse pro-B cell lines, dispensable for joining CSR-associated DSBs in a cycling mouse B cell line, and dispensable for normal IR-resistance in both G1-arrested and cycling pro-B lines. However, we find that combined deficiency for PAXX and XLF in G1-arrested pro-B lines abrogates DSB joining during V(D)J recombination and sensitizes the cells to IR exposure. Thus, PAXX provides core C-NHEJ factor-associated functions in the absence of XLF and vice versa in G1-arrested Pro-B cell lines. Finally, we also find that PAXX-deficiency has no impact on V(D)J recombination DSB joining in ATM-deficient pro-B lines. We discuss implications of these findings with respect to potential PAXX and XLF functions in C-NHEJ.
 
Overall design Examination of CSR Switch mu-to-alpha junctions from mu bait DSBs using LAM-HTGTS and Illumina Miseq. Two clones of PAXX-/- and XLF-/- and 1 clone of Ligase4-/- were derived from the parental CH12F3 line; the second Ligase4-/- clone was acquired from Kefei Yu. Two clones of XLF-/-PAXX-/-CH12 cells were derived from one of the PAXX-/- clones. Three biological replicates were analyzed for each clone.
 
Contributor(s) Kumar V, Frock RL, Alt FW
Citation(s) 27601633
Submission date Jul 06, 2016
Last update date May 15, 2019
Contact name Richard L Frock
E-mail(s) frock@stanford.edu
Organization name Stanford University
Department Radiation Oncology
Lab Frock Lab
Street address 269 Campus Drive
City Stanford
State/province California
ZIP/Postal code 94305
Country USA
 
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (27)
GSM2227255 CSR_Im_WT_Rep1
GSM2227256 CSR_Im_WT_Rep2
GSM2227257 CSR_Im_WT_Rep3
Relations
BioProject PRJNA328026
SRA SRP077999

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
GSE84102_CSR_Im_Ligase4_1.txt.gz 2.3 Mb (ftp)(http) TXT
GSE84102_CSR_Im_Ligase4_2.txt.gz 1.2 Mb (ftp)(http) TXT
GSE84102_CSR_Im_PAXX_1.txt.gz 1.2 Mb (ftp)(http) TXT
GSE84102_CSR_Im_PAXX_2.txt.gz 925.3 Kb (ftp)(http) TXT
GSE84102_CSR_Im_WT.txt.gz 642.0 Kb (ftp)(http) TXT
GSE84102_CSR_Im_XLF_1.txt.gz 1.2 Mb (ftp)(http) TXT
GSE84102_CSR_Im_XLF_2.txt.gz 997.5 Kb (ftp)(http) TXT
GSE84102_CSR_Im_XLF_PAXX_1.txt.gz 1.4 Mb (ftp)(http) TXT
GSE84102_CSR_Im_XLF_PAXX_2.txt.gz 1.3 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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