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dc.contributor.authorSchenten, Dominik
dc.contributor.authorKracker, Sven
dc.contributor.authorEsposito, Gloria
dc.contributor.authorFranco, Sonia
dc.contributor.authorKlein, Ulf
dc.contributor.authorMurphy, Michael C.
dc.contributor.authorAlt, Frederick W.
dc.contributor.authorRajewsky, Klaus
dc.date.accessioned2011-03-29T16:18:49Z
dc.date.issued2009
dc.identifier.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.en_US
dc.identifier.issn0022-1007en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4777439
dc.description.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.en_US
dc.language.isoen_USen_US
dc.publisherRockefeller University Pressen_US
dc.relation.isversionofdoi:10.1084/jem.20080669en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646585/pdf/en_US
dash.licenseLAA
dc.titlePolζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stabilityen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Experimental Medicineen_US
dash.depositing.authorAlt, Frederick W.
dc.date.available2011-03-29T16:18:49Z
dash.affiliation.otherHMS^Geneticsen_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Pediatrics-Children's Hospitalen_US
dc.identifier.doi10.1084/jem.20080669*
dash.contributor.affiliatedMurphy, Michael
dash.contributor.affiliatedRajewsky, Klaus
dash.contributor.affiliatedAlt, Frederick


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