| First Author | Langerak P | Year | 2007 |
| Journal | J Exp Med | Volume | 204 |
| Issue | 8 | Pages | 1989-98 |
| PubMed ID | 17664295 | Mgi Jnum | J:125916 |
| Mgi Id | MGI:3760195 | Doi | 10.1084/jem.20070902 |
| Citation | Langerak P, et al. (2007) A/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification. J Exp Med 204(8):1989-98 |
| abstractText | B cells use translesion DNA synthesis (TLS) to introduce somatic mutations around genetic lesions caused by activation-induced cytidine deaminase. Monoubiquitination at lysine(164) of proliferating cell nuclear antigen (PCNA(K164)) stimulates TLS. To determine the role of PCNA(K164) modifications in somatic hypermutation, PCNA(K164R) knock-in mice were generated. PCNA(K164R/K164R) mutants are born at a sub-Mendelian frequency. Although PCNA(K164R/K164R) B cells proliferate and class switch normally, the mutation spectrum of hypermutated immunoglobulin (Ig) genes alters dramatically. A strong reduction of mutations at template A/T is associated with a compensatory increase at G/C, which is a phenotype similar to polymerase eta (Poleta) and mismatch repair-deficient B cells. Mismatch recognition, monoubiquitinated PCNA, and Poleta likely cooperate in establishing mutations at template A/T during replication of Ig genes. |
