Mutations Specific to the Xeroderma Pigmentosum Group E Ddb− Phenotype

doi:10.1074/jbc.271.40.24317

Mutations Specific to the Xeroderma Pigmentosum Group E Ddb⁻ Phenotype*

From the Division of Biochemistry and Molecular Biology, University of California, Berkeley, California 94720-3202

^‡ To whom correspondence should be addressed:
Division of Biochemistry and Molecular Biology, Barker Hall, University of California, Berkeley, CA 94720-3202
. Tel.: 510-642-7583; Fax: 510-643-5035; E-mail: linn{at}mendel.berkeley.edu.

Abstract

The activity of a damage-specific DNA-binding protein (DDB) is absent from a subset, Ddb⁻, of cell strains from patients with xeroderma pigmentosum group E (XP-E). DDB is a heterodimer of 127-kDa and 48-kDa subunits. We have now identified single-base mutations in the gene of the 48-kDa subunit in cells from the three known Ddb⁻ individuals, but not in XP-E strains that have the activity. An A → G transition causes a K244E change in XP82TO and a G → A transition causes an R273H change in XP2RO and XP3RO. No mutations were found in the cDNA of the 127-kDa subunit. Overexpression of p48 in insect cells greatly increases DDB activity in the cells, especially if p127 is jointly overexpressed. These results demonstrate that p48 is required for DNA binding activity, but at the same time necessitate further definition of the genetic basis of XP group E.

Footnotes

↵* This work was supported by U. S. Department of Energy Grant FG03-92ER61458 and by an Alexander Hollaender Postdoctoral Fellowship (to A. F. N.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

DDB

damage-specific DNA-binding protein

XP-E

xeroderma pigmentosum group E

DDb⁺

DDB activity present

Ddb⁻

DDB activity absent

UTR

untranslated region of cDNA

RT

reverse transcription

PCR

polymerase chain reaction

bp

base pair(s).
↵² A. Kazantsev and A. Sancar, personal communication.
- Received July 26, 1996.