the fanconi anemia core complex is dispensable during somatic hypermutation and class switch recombination在体细胞hypermutation fanconi贫血核心情结是可有可无的重组和类开关.pdfVIP

The Fanconi Anemia Core Complex Is Dispensable during Somatic Hypermutation and Class Switch Recombination Peter H. L. Krijger, Niek Wit, Paul C. M. van den Berk, Heinz Jacobs* Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands 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. Citation: Krijger PHL, Wit N, van den Berk PCM, Jacobs H (2010) The Fanconi Anemia Core Complex Is Dispensable during Somatic Hypermutation and Class Switch Recombination. PLoS ONE 5(12): e15236. doi:10.1371/journal.pone.0015236 Editor: Reuben S. Harris, University of Minnesota, United States of America Received October 5, 2010; Accepted October 31, 2010; Published December 29, 2010 Copyright: 2010 Krijger et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Li