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Altered Ig hypermutation pattern and frequency in complementary mouse models of DNA polymerase ? activity.

ABSTRACT: To test the hypothesis that DNA polymerase ? participates in Ig hypermutation, we generated two mouse models of Pol ? function: a B cell-specific conditional knockout and a knock-in strain with a Pol ? mutagenesis-enhancing mutation. Pol ?-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 ? 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 ?. Combined, these data are best explained by a direct role for DNA polymerase ? in Ig hypermutation.

SUBMITTER: Daly J

PROVIDER: S-EPMC3358437 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Altered Ig hypermutation pattern and frequency in complementary mouse models of DNA polymerase ζ activity.

Daly Janssen J Bebenek Katarzyna K Watt Danielle L DL Richter Kathleen K Jiang Chuancang C Zhao Ming-Lang ML Ray Madhumita M McGregor W Glenn WG Kunkel Thomas A TA Diaz Marilyn M

Journal of immunology (Baltimore, Md. : 1950) 20120430 11

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 ...[more]

PMID: 22547703

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