title: The DNA glycosylases Ogg1 and Nth1 do not contribute to Ig class switching in activated mouse splenic B cells.
abstract: During activation of B cells to undergo class switching, B cell metabolism is increased, and levels of reactive oxygen species (ROS) are increased. ROS can oxidize DNA bases resulting in substrates for the DNA glycosylases Ogg1 and Nth1. Ogg1 and Nth1 excise oxidized bases, and nick the resulting abasic sites, forming single-strand DNA breaks (SSBs) as intermediates during the repair process. In this study, we asked whether splenic B cells from mice deficient in these two enzymes would show altered class switching and decreased DNA breaks in comparison with wild-type mice. As the c-myc gene frequently recombines with the IgH S region in B cells induced to undergo class switching, we also analyzed the effect of deletion of these two glycosylases on DSBs in the c-myc gene. We did not detect a reduction in S region or c-myc DSBs or in class switching in splenic B cells from Ogg1- or Nth1-deficient mice or from mice deficient in both enzymes.
authors.affiliation: Department of Microbiology and Physiological Systems, Medical School, University of Massachusetts, Worcester, Massachusetts, United States of America.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Ucher
authors.forename: Erin K
authors.initials: EK
authors.lastname: Linehan
authors.forename: George W
authors.initials: GW
authors.lastname: Teebor
authors.forename: Carol E
authors.initials: CE
authors.lastname: Schrader
authors.forename: Janet
authors.initials: J
authors.lastname: Stavnezer
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D045647:DNA Glycosylases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000172:deficiency* / Q000235:genetics; D055786:Gene Knockout Techniques; D016259:Genes, myc; D017578:Immunoglobulin Class Switching; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D011995:Recombination, Genetic; D013154:Spleen / Q000166:cytology*; D014158:Transcription, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains; D043224:Deoxyribonuclease (Pyrimidine Dimer); C470703:Nthl1 protein, mouse; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse