title: Normal hypermutation in antibody genes from congenic mice defective for DNA polymerase iota.
abstract: Several low fidelity DNA polymerases participate in generating mutations in immunoglobulin genes. Polymerase eta is clearly involved in the process by causing substitutions of A:T base pairs, whereas polymerase iota has a controversial role. Although the frequency of mutations was decreased in the BL2 cell line deficient for polymerase iota, hypermutation was normal in the 129 strain of mice, which has a natural nonsense mutation in the Poli gene. It is possible that the mice compensated for the defect over time, or that polymerase eta substituted in the absence of polymerase iota. To examine polymerase iota in a genetically defined background, we backcrossed the 129 nonsense mutation to the C57BL/6 strain for six generations. Class switch recombination and hypermutation were studied in these mice and in congenic mice doubly deficient for both polymerases iota and eta. The absence of both polymerases did not affect production of IgG1, indicating that these enzymes are not involved in switch recombination. Poli(-/-F6) mice had the same types of nucleotide substitutions in variable genes as their C57BL/6 counterparts, and mice doubly deficient for polymerases iota and eta had the same mutational spectrum as Polh-/- mice. Thus, polymerase iota did not contribute to the mutational spectra, even in the absence of polymerase eta.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Stella A
authors.initials: SA
authors.lastname: Martomo
authors.forename: William W
authors.initials: WW
authors.lastname: Yang
authors.forename: Alexandra
authors.initials: A
authors.lastname: Vaisman
authors.forename: Alex
authors.initials: A
authors.lastname: Maas
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokoi
authors.forename: Jan H
authors.initials: JH
authors.lastname: Hoeijmakers
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
authors.forename: Roger
authors.initials: R
authors.lastname: Woodgate
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Gearhart
mesh_terms: D000818:Animals; D001483:Base Sequence; D018389:Codon, Nonsense; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000502:physiology*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000094769:DNA Polymerase iota; D000099270:Y-Family DNA Polymerases
chemical_list: D018389:Codon, Nonsense; D004259:DNA-Directed DNA Polymerase; D007074:Immunoglobulin G; D000094769:DNA Polymerase iota; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases