Dependence of nucleotide substitutions on Ung2, Msh2, and PCNA-Ub during somatic hypermutation

• DOI: 10.1084/jem.20091707
• Publication Date: 2009-11-10T03:06:01Z
• Authors: Peter H.L. Krijger; Petra Langerak; Paul C.M. van den...; Heinz Jacobs
• Keywords: MSH2; Uracil-DNA glycosylase

During somatic hypermutation (SHM), B cells introduce mutations into their immunoglobulin genes to generate high affinity antibodies. Current models suggest a separation in the generation of G/C transversions by Ung2-dependent pathway and A/T Msh2/ubiquitinated proliferating cell nuclear antigen (PCNA-Ub)–dependent pathway. It is currently unknown whether these pathways compete initiate mutagenesis PCNA-Ub functions downstream Ung2. Furthermore, do not explain why mice lacking Msh2 have more than twofold reduction total mutation frequency. Our data indicate that required for both we provide evidence are noncompetitive even collaborate half all transversions. These findings significantly add our understanding SHM necessitate an update present models.