| First Author | Iguchi M | Year | 2014 |
| Journal | Oncogene | Volume | 33 |
| Issue | 27 | Pages | 3612-7 |
| PubMed ID | 23955086 | Mgi Jnum | J:212610 |
| Mgi Id | MGI:5581879 | Doi | 10.1038/onc.2013.331 |
| Citation | Iguchi M, et al. (2014) The error-prone DNA polymerase iota provides quantitative resistance to lung tumorigenesis and mutagenesis in mice. Oncogene 33(27):3612-7 |
| abstractText | Opposite undamaged nucleotide T, DNA polymerase iota (Poliota) preferentially incorporates G rather than A, violating the Watson-Crick rule. Although the actual biological role of Poliota remains enigmatic, we have identified its coding gene as a candidate for pulmonary adenoma resistance 2 (Par2), a mouse quantitative trait locus modulating chemically induced lung tumor susceptibility. Notably, the most tumor-sensitive Par2 allele possessed by the 129X1/SvJ mouse is associated with a loss-of-function mutation in Poliota. To determine whether the nonfunctional Poliota is responsible for the 129X1/SvJ-specific Par2 phenotype, we knocked out Poliota in a C57BL/6J mouse carrying a less tumor-sensitive Par2 allele. Disruption of the C57BL/6J Poliota conferred 129X1/SvJ-like sensitivity on the C57BL/6J Par2 locus and increased the in vivo mutation frequency in the lung, providing definitive proof that Poliota causes the Par2 effect and inhibits tumorigenesis and mutagenesis, despite its extreme replication infidelity. |
