UV-B radiation induces epithelial tumors in mice lacking DNA polymerase η and mesenchymal tumors in mice deficient for DNA polymerase ι

Tsuyoshi Ohkumo, Yuji Kondo, Masayuki Yokoi, Tetsuya Tsukamoto, Ayumi Yamada, Taiki Sugimoto, Rie Kanao, Yujiro Higashi, Hisato Kondoh, Masae Tatematsu, Chikahide Masutani, Fumio Hanaoka

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)

Abstract

DNA polymerase η (Pol η) is the product of the Polh gene, which is responsible for the group variant of xeroderma pigmentosum, a rare inherited recessive disease which is characterized by susceptibility to sunlight-induced skin cancer. We recently reported in a study of Polh mutant mice that Pol η is involved in the somatic hypermutation of immunoglobulin genes, but the cancer predisposition of Polh-/- mice has not been examined until very recently. Another translesion synthesis polymerase, Pol ι, a Pol η paralog encoded by the Poli gene, is naturally deficient in the 129 mouse strain, and the function of Pol ι is enigmatic. Here, we generated Polh Poli double-deficient mice and compared the tumor susceptibility of them with Polh- or Poli-deficient animals under the same genetic background. While Pol ι deficiency does not influence the UV sensitivity of mouse fibroblasts irrespective of Polh genotype, Polh Poli double-deficient mice show slightly earlier onset of skin tumor formation. Intriguingly, histological diagnosis after chronic treatment with UV light reveals that Pol ι deficiency leads to the formation of mesenchymal tumors, such as sarcomas, that are not observed in Polh-/- mice. These results suggest the involvement of the Pol η and Pol ι proteins in UV-induced skin carcinogenesis.

Original languageEnglish
Pages (from-to)7696-7706
Number of pages11
JournalMolecular and Cellular Biology
Volume26
Issue number20
DOIs
Publication statusPublished - 10-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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