| First Author | Saribasak H | Year | 2012 |
| Journal | J Exp Med | Volume | 209 |
| Issue | 6 | Pages | 1075-81 |
| PubMed ID | 22615128 | Mgi Jnum | J:189124 |
| Mgi Id | MGI:5444369 | Doi | 10.1084/jem.20112234 |
| Citation | Saribasak H, et al. (2012) DNA polymerase zeta generates tandem mutations in immunoglobulin variable regions. J Exp Med 209(6):1075-81 |
| abstractText | Low-fidelity DNA polymerases introduce nucleotide substitutions in immunoglobulin variable regions during somatic hypermutation. Although DNA polymerase (pol) eta is the major low-fidelity polymerase, other DNA polymerases may also contribute. Existing data are contradictory as to whether pol zeta is involved. We reasoned that the presence of pol eta may mask the contribution of pol zeta, and therefore we generated mice deficient for pol eta and heterozygous for pol zeta. The frequency and spectra of hypermutation was unaltered between Polzeta(+/-) Poleta(-/-) and Polzeta(+/+) Poleta(-/-) clones. However, there was a decrease in tandem double-base substitutions in Polzeta(+/-) Poleta(-/-) cells compared with Polzeta(+/+) Poleta(-/-) cells, suggesting that pol zeta generates tandem mutations. Contiguous mutations are consistent with the biochemical property of pol zeta to extend a mismatch with a second mutation. The presence of this unique signature implies that pol zeta contributes to mutational synthesis in vivo. Additionally, data on tandem mutations from wild type, Polzeta(+/-), Polzeta(-/-), Ung(-/-), Msh2(-/-), Msh6(-/-), and Ung(-/-) Msh2(-/-) clones suggest that pol zeta may function in the MSH2-MSH6 pathway. |
