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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Vydané v:	PloS one Ročník 5; číslo 12; s. e15236
Hlavní autori:	Krijger, Peter H. L., Wit, Niek, van den Berk, Paul C. M., Jacobs, Heinz
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 29.12.2010 Public Library of Science (PLoS)
Predmet:	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
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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