The Fanconi Anemia Core Complex Is Dispensable during Somatic Hypermutation and Class Switch Recombination

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 tra...

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Published in:PloS one Vol. 5; no. 12; p. e15236
Main Authors: Krijger, Peter H. L., Wit, Niek, van den Berk, Paul C. M., Jacobs, Heinz
Format: Journal Article
Language:English
Published: United States Public Library of Science 29.12.2010
Public Library of Science (PLoS)
Subjects:
Analysis
Anemia
Animals
Antibodies
Antigens
B cells
B-Lymphocytes - cytology
Biology
Cancer
Chemical synthesis
Cisplatin - pharmacology
Class switching
Cross-Linking Reagents - pharmacology
Crosslinking
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA biosynthesis
DNA Mutational Analysis
DNA polymerases
DNA repair
DNA-directed DNA polymerase
Fanconi Anemia - metabolism
Fanconi syndrome
Fanconi's anemia
Fibroblasts - cytology
Genes
Genotype
Immune response
Immune system
Immunoglobulin Class Switching
Immunoglobulins
Immunology
Lymphocytes B
Mice
Mutagenesis
Mutation
Phenotype
Proliferating cell nuclear antigen
Recombination
Rodents
Somatic hypermutation
Ubiquitin - chemistry
Ubiquitination
Ultraviolet Rays
Netherlands
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary: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.
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Conceived and designed the experiments: PHLK HJ. Performed the experiments: PHLK NW PCB. Analyzed the data: PHLK HJ. Wrote the paper: PHLK HJ. Edited the paper: PHLK HJ.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0015236