First Author | Phung QH | Year | 1998 |
Journal | J Exp Med | Volume | 187 |
Issue | 11 | Pages | 1745-51 |
PubMed ID | 9607916 | Mgi Jnum | J:110877 |
Mgi Id | MGI:3641481 | Doi | 10.1084/jem.187.11.1745 |
Citation | Phung QH, et al. (1998) Increased hypermutation at G and C nucleotides in immunoglobulin variable genes from mice deficient in the MSH2 mismatch repair protein. J Exp Med 187(11):1745-51 |
abstractText | Rearranged immunoglobulin variable genes are extensively mutated after stimulation of B lymphocytes by antigen. Mutations are likely generated by an error-prone DNA polymerase, and the mismatch repair pathway may process the mispairs. To examine the role of the MSH2 mismatch repair protein in hypermutation, Msh2-/- mice were immunized with oxazolone, and B cells were analyzed for mutation in their VkappaOx1 light chain genes. The frequency of mutation in the repair-deficient mice was similar to that in Msh2+/+ mice, showing that MSH2-dependent mismatch repair does not cause hypermutation. However, there was a striking bias for mutations to occur at germline G and C nucleotides. The results suggest that the hypermutation pathway frequently mutates G.C pairs, and a MSH2-dependent pathway preferentially corrects mismatches at G and C. |