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Molecular and Cellular Biology, October 2006, p. 7696-7706, Vol. 26, No. 20
0270-7306/06/$08.00+0     doi:10.1128/MCB.01076-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase {eta} and Mesenchymal Tumors in Mice Deficient for DNA Polymerase {iota}

Tsuyoshi Ohkumo,1,2,{dagger} Yuji Kondo,1,3,{dagger} Masayuki Yokoi,1,4,{dagger} Tetsuya Tsukamoto,5 Ayumi Yamada,1,3 Taiki Sugimoto,1,3 Rie Kanao,1,3 Yujiro Higashi,6 Hisato Kondoh,6 Masae Tatematsu,5 Chikahide Masutani,1,4 and Fumio Hanaoka1,3,4,7*

Cellular Biology Laboratory, Graduate School of Frontier Biosciences,1 Graduate School of Medicine,2 Graduate School of Pharmaceutical Sciences, Osaka University, Osaka,3 Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Saitama,4 Division of Oncological Pathology, Aich Cancer Center Research Institute, Nagoya,5 Developmental Biology Laboratory, Graduate School of Frontier Biosciences, Osaka University, Osaka,6 Cellular Physiology Laboratory, RIKEN Discovery Research Institute, Saitama, Japan7

Received 15 June 2006/ Returned for modification 10 July 2006/ Accepted 25 July 2006

DNA polymerase {eta} (Pol {eta}) 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 {eta} 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 {iota}, a Pol {eta} paralog encoded by the Poli gene, is naturally deficient in the 129 mouse strain, and the function of Pol {iota} 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 {iota} 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 {iota} 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 {eta} and Pol {iota} proteins in UV-induced skin carcinogenesis.

* Corresponding author. Mailing address: Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-7975. Fax: 81-6-6877-9382. E-mail: fhanaoka{at}fbs.osaka-u.ac.jp.

{dagger} T.O., Y.K., and M.Y. contributed equally to this work.

Molecular and Cellular Biology, October 2006, p. 7696-7706, Vol. 26, No. 20
0270-7306/06/$08.00+0     doi:10.1128/MCB.01076-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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