title: Altered Ig hypermutation pattern and frequency in complementary mouse models of DNA polymerase ζ activity.
abstract: To test the hypothesis that DNA polymerase ζ participates in Ig hypermutation, we generated two mouse models of Pol ζ function: a B cell-specific conditional knockout and a knock-in strain with a Pol ζ mutagenesis-enhancing mutation. Pol ζ-deficient B cells had a reduction in mutation frequency at Ig loci in the spleen and in Peyer's patches, whereas knock-in mice with a mutagenic Pol ζ displayed a marked increase in mutation frequency in Peyer's patches, revealing a pattern that was similar to mutations in yeast strains with a homologous mutation in the gene encoding the catalytic subunit of Pol ζ. Combined, these data are best explained by a direct role for DNA polymerase ζ in Ig hypermutation.
authors.affiliation: Somatic Hypermutation Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Janssen
authors.initials: J
authors.lastname: Daly
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bebenek
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Watt
authors.forename: Kathleen
authors.initials: K
authors.lastname: Richter
authors.forename: Chuancang
authors.initials: C
authors.lastname: Jiang
authors.forename: Ming-Lang
authors.initials: ML
authors.lastname: Zhao
authors.forename: Madhumita
authors.initials: M
authors.lastname: Ray
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McGregor
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
authors.forename: Marilyn
authors.initials: M
authors.lastname: Diaz
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D055879:Gene Knock-In Techniques; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics* / Q000276:immunology*
chemical_list: D004259:DNA-Directed DNA Polymerase; C425929:DNA polymerase zeta; C486862:REV3L protein, mouse