Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability
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CitationSchenten, Dominik, Sven Kracker, Gloria Esposito, Sonia Franco, Ulf Klein, Michael Murphy, Frederick W. Alt, and Klaus Rajewsky. 2009. Polζ ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability. Journal of Experimental Medicine 206(2): 477-490.
AbstractPolζ is an error-prone DNA polymerase that is critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) and possible contribution to DNA double-strand break (DSB) repair in class switch recombination (CSR), we ablated Rev3, the catalytic subunit of Polζ, selectively in mature B cells in vivo. The frequency of somatic mutation was reduced in the mutant cells but the pattern of SHM was unaffected. Rev3-deficient B cells also exhibited pronounced chromosomal instability and impaired proliferation capacity. Although the data thus argue against a direct role of Polζ in SHM, Polζ deficiency directly interfered with CSR in that activated Rev3-deficient B cells exhibited a reduced efficiency of CSR and an increased frequency of DNA breaks in the immunoglobulin H locus. Based on our results, we suggest a nonredundant role of Polζ in DNA DSB repair through nonhomologous end joining.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4777439
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