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Abnormal regulation of DDB2 gene expression in xeroderma pigmentosum group E strains

Oncogene volume 20, pages 7041–7050 (2001)Cite this article

Abstract

A damage-specific DNA binding protein (DDB) activity is absent from a subset (DDB−) of cells from individuals initially classified as group E of xeroderma pigmentosum (XP), a hereditary, photosensitive disease with a high incidence of skin malignancies. In these cases, mutations have been identified in the DDB2 gene (DDB2−) that codes for the small subunit, p48, of the DDB heterodimer. In four DDB2−strains, neither p48 nor DDB activity were observed before or after UV-irradiation, despite an unusually strong up-regulation of DDB2 mRNA levels after UV-irradiation. In a fifth strain, XP82TO, p48 was detectable and both DDB2 mRNA and p48 levels were more up-regulated after UV-irradiation than in normal primary cells. Moreover, DDB activity also became apparent after irradiation. XP82TO showed very mild clinical manifestations compared with the other DDB− patients. These results, coupled with our findings that most, if not all DDB+ cells classified as XP-E were misclassified, suggests a direct correlation between DDB2 levels and the XP-E phenotype.

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Abbreviations

DDB:

damage-specific DNA binding protein

NER:

nucleotide excision repair

UDS:

unscheduled DNA synthesis

XP:

xeroderma pigmentosum

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Acknowledgements

We thank Dr M Swift (New York Medical College) and Dr JE Cleaver (University of California, San Francisco) for personal communications, Dr JHJ Hoeijmakers (Erasmus University, Rotterdam) for providing cells, Drs Francesca Zolezzi and Hitomi Asahara (University of California, Berkeley) for helpful discussions, Miss Ann Fischer (Berkeley Tissue Culture Facility) for helping with cell culture, and Mrs Yuka Itoh for encouragement. This work was supported by the Nakatomi Foundation (to T Itoh), and by USPHS grants P30ES08196 and GM59424 (to S Linn).

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  1. Division of Biochemistry and Molecular Biology, 229 Stanley Hall, University of California, Berkeley, CA 94720-3206, California, USA

    Toshiki Itoh, Anne Nichols & Stuart Linn

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  1. Toshiki Itoh
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Correspondence to Toshiki Itoh or Stuart Linn.

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Itoh, T., Nichols, A. & Linn, S. Abnormal regulation of DDB2 gene expression in xeroderma pigmentosum group E strains. Oncogene 20, 7041–7050 (2001). https://doi.org/10.1038/sj.onc.1204909

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