TY - JOUR
T1 - UV-B radiation induces epithelial tumors in mice lacking DNA polymerase η and mesenchymal tumors in mice deficient for DNA polymerase ι
AU - Ohkumo, Tsuyoshi
AU - Kondo, Yuji
AU - Yokoi, Masayuki
AU - Tsukamoto, Tetsuya
AU - Yamada, Ayumi
AU - Sugimoto, Taiki
AU - Kanao, Rie
AU - Higashi, Yujiro
AU - Kondoh, Hisato
AU - Tatematsu, Masae
AU - Masutani, Chikahide
AU - Hanaoka, Fumio
PY - 2006/10
Y1 - 2006/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33749602964&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749602964&partnerID=8YFLogxK
U2 - 10.1128/MCB.01076-06
DO - 10.1128/MCB.01076-06
M3 - Article
C2 - 17015482
AN - SCOPUS:33749602964
SN - 0270-7306
VL - 26
SP - 7696
EP - 7706
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 20
ER -