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  • Original Paper
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Tumor-prone phenotype of the DDB2-deficient mice

Oncogene volume 24, pages 469–478 (2005)Cite this article

Abstract

DDB2 is an essential subunit of the damaged-DNA recognition factor DDB, which is involved in global genomic repair in human cells. Moreover, DDB2 is mutated in the repair-deficiency disease xeroderma pigmentosum (Group E). Expression of DDB2 in human cells is induced by P53, BRCA1 and by ionizing radiation. The DDB2 protein associates with transcriptional activator and coactivator proteins. In addition, DDB2 in conjunction with DDB1 associates with cullin 4A and the Cop9/signalosome. We generated a mouse strain deficient for DDB2 (DDB2−/−). Consistent with the human disease (XP-E), the DDB2−/− mice were susceptible to UV-induced skin carcinogenesis. We observed a significant difference in the initial rate of cyclobutane pyrimidine dimer (CPD)-removal from the skin following UV irradiation. Also, the DDB2-deficient mice exhibited a significantly reduced life span compared to their wild-type littermates. Moreover, unlike other XP-deficient mice, the DDB2-deficient mice developed spontaneous malignant tumors at a high rate between the ages of 20 and 25 months. The observations suggest that, in addition to DNA repair, the other interactions of DDB2 are significant in its tumor suppression function.

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Acknowledgements

We thank Dr S Linn (UC, Berkeley) for helping us with reagents. We thank the UIC Transgenic Facility for blastocyst injections. HK is supported by a grant from the NCI (1R01CA100204) and a grant from the DOD (DAMD 17-02-1-0413). This work was supported by grants from the NCI (CA 77637 and CA 88863) to PR.

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  1. Amit Chakrabortty

    Present address: Hindustan Lever Limited, Mumbai, 400 099, India

Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, IL, 60607, USA

    Taewon Yoon, Amit Chakrabortty, Roberta Franks, Hiroaki Kiyokawa & Pradip Raychaudhuri

  2. College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, 61802-2439, USA

    Ted Valli

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Correspondence to Pradip Raychaudhuri.

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Yoon, T., Chakrabortty, A., Franks, R. et al. Tumor-prone phenotype of the DDB2-deficient mice. Oncogene 24, 469–478 (2005). https://doi.org/10.1038/sj.onc.1208211

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