title: The Fanconi anemia core complex is dispensable during somatic hypermutation and class switch recombination.
abstract: To generate high affinity antibodies during an immune response, B cells undergo somatic hypermutation (SHM) of their immunoglobulin genes. Error-prone translesion synthesis (TLS) DNA polymerases have been reported to be responsible for all mutations at template A/T and at least a fraction of G/C transversions. In contrast to A/T mutations which depend on PCNA ubiquitination, it remains unclear how G/C transversions are regulated during SHM. Several lines of evidence indicate a mechanistic link between the Fanconi Anemia (FA) pathway and TLS. To investigate the contribution of the FA pathway in SHM we analyzed FancG-deficient B cells. B cells deficient for FancG, an essential member of the FA core complex, were hypersensitive to treatment with cross-linking agents. However, the frequencies and nucleotide exchange spectra of SHM remained comparable between wild-type and FancG-deficient B cells. These data indicate that the FA pathway is not involved in regulating the outcome of SHM in mammals. In addition, the FA pathway appears dispensable for class switch recombination.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Peter H L
authors.initials: PH
authors.lastname: Krijger
authors.forename: Niek
authors.initials: N
authors.lastname: Wit
authors.forename: Paul C M
authors.initials: PC
authors.lastname: van den Berk
authors.forename: Heinz
authors.initials: H
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004252:DNA Mutational Analysis; D005199:Fanconi Anemia / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D005838:Genotype; D017578:Immunoglobulin Class Switching; D051379:Mice; D009154:Mutation; D010641:Phenotype; D025801:Ubiquitin / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D025801:Ubiquitin; D004247:DNA; D002945:Cisplatin