title: Normal immunoglobulin gene somatic hypermutation in Pol kappa-Pol iota double-deficient mice.
abstract: Somatic hypermutation (SHM) occurs in the variable region of immunoglobulin genes in germinal center B cells where it plays an important role in affinity maturation of the T cell-dependent immune response. Although the precise mechanism of SHM is still unknown, it has been suggested that error-prone DNA polymerases (Pol) are involved in SHM. Poliota is a member of the error-prone Y-family of DNA polymerases which exhibit translesion synthesis activity in vitro and are highly mutagenic when replicating on non-damaged DNA templates. In BL2 cell line stimulated to induce SHM, the induction is Poliota-dependent. However, in 129-derived strains of mice deficient in Poliota, SHM is normal. One possible explanation for this discrepancy is that a Poliota deficiency in mice might be compensated for by another error-prone DNA polymerase, such as Polkappa, which also belongs to the Y-family of DNA polymerases. Although SHM in Polkappa-deficient mice is normal, their deficiency might be compensated for by Poliota. In this study, we generated Polkappa-Poliota double-deficient mice and examined them for SHM. We found that the double-deficient mice had the normal SHM frequency and profile, rendering them indistinguishable from Polkappa-deficient mice and thus conclude that Poliota and Polkappa are dispensable for SHM in mice.
authors.affiliation: Division of Biosignaling, Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Takachika
authors.initials: T
authors.lastname: Azuma
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanjo
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Haruo
authors.initials: H
authors.lastname: Ohmori
mesh_terms: D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D005803:Genes, Immunoglobulin / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000094769:DNA Polymerase iota; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; D000094769:DNA Polymerase iota; C498613:Polk protein, mouse; D000099270:Y-Family DNA Polymerases