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Mol Cell Biol, July 1998, p. 4391-4399, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

Byung Joon Hwang,1 Stephanie Toering,1 Uta Francke,2 and Gilbert Chu1 *

Departments of Medicine and Biochemistry1 and Howard Hughes Medical Institute and Department of Genetics,2 Stanford University School of Medicine, Stanford, California 94305

Received 8 September 1997/Returned for modification 23 October 1997/Accepted 19 March 1998

A subset of xeroderma pigmentosum (XP) group E cells lack a factor that binds to DNA damaged by UV radiation. This factor can be purified to homogeneity as p125, a 125-kDa polypeptide. However, when cDNA encoding p125 is translated in vitro, only a small fraction binds to UV-damaged DNA, suggesting that a second factor is required for the activation of p125. We discovered that most hamster cell lines expressed inactive p125, which was activated in somatic cell hybrids containing human chromosome region 11p11.2-11cen. This region excluded p125 but included p48, which encodes a 48-kDa polypeptide known to copurify with p125 under some conditions. Expression of human p48 activated p125 binding in hamster cells and increased p125 binding in human cells. No such effects were observed from expression of p48 containing single amino acid substitutions from XP group E cells that lacked binding activity, demonstrating that the p48 gene is defective in those cells. Activation of p125 occurred by a "hit-and-run" mechanism, since the presence of p48 was not required for subsequent binding. Nevertheless, p48 was capable of forming a complex with p125 either bound to UV-damaged DNA or in free solution. It is notable that hamster cells fail to efficiently repair cyclobutane pyrimidine dimers in nontranscribed DNA and fail to express p48, which contains a WD motif with homology to proteins that reorganize chromatin. We propose that p48 plays a role in repairing lesions that would otherwise remain inaccessible in nontranscribed chromatin.

* Corresponding author. Mailing address: M-211, Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, CA 94305. Phone: (650) 725-6442. Fax: (650) 725-1420. E-mail: chu{at}cmgm.stanford.edu.

Mol Cell Biol, July 1998, p. 4391-4399, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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