Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability
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Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability
| Title: | Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability |
| Author: |
Schenten, Dominik; Kracker, Sven; Esposito, Gloria; Franco, Sonia; Klein, Ulf; Murphy, Michael C.; Alt, Frederick W.; Rajewsky, Klaus
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Schenten, 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. |
| Full Text & Related Files: |
2646585.pdf (4.953Mb; PDF) 
|
| Abstract: | Polζ 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. |
| Published Version: | doi:10.1084/jem.20080669 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646585/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4777439 |
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