dc.contributor.author | Schenten, Dominik | |
dc.contributor.author | Kracker, Sven | |
dc.contributor.author | Esposito, Gloria | |
dc.contributor.author | Franco, Sonia | |
dc.contributor.author | Klein, Ulf | |
dc.contributor.author | Murphy, Michael C. | |
dc.contributor.author | Alt, Frederick W. | |
dc.contributor.author | Rajewsky, Klaus | |
dc.date.accessioned | 2011-03-29T16:18:49Z | |
dc.date.issued | 2009 | |
dc.identifier.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. | en_US |
dc.identifier.issn | 0022-1007 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4777439 | |
dc.description.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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Rockefeller University Press | en_US |
dc.relation.isversionof | doi:10.1084/jem.20080669 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646585/pdf/ | en_US |
dash.license | LAA | |
dc.title | Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | Journal of Experimental Medicine | en_US |
dash.depositing.author | Alt, Frederick W. | |
dc.date.available | 2011-03-29T16:18:49Z | |
dash.affiliation.other | HMS^Genetics | en_US |
dash.affiliation.other | HMS^Pediatrics-Children's Hospital | en_US |
dash.affiliation.other | HMS^Pathology | en_US |
dash.affiliation.other | HMS^Pediatrics-Children's Hospital | en_US |
dc.identifier.doi | 10.1084/jem.20080669 | * |
dash.contributor.affiliated | Murphy, Michael | |
dash.contributor.affiliated | Rajewsky, Klaus | |
dash.contributor.affiliated | Alt, Frederick | |