Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair

Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair

^*Departments of Medicine and Biochemistry and ^‡Department of Biological Sciences, Stanford University School of Medicine, Stanford, CA 94305-5115

Contributed by Philip Hanawalt

Abstract

In human cells, efficient global genomic repair of DNA damage induced by ultraviolet radiation requires the p53 tumor suppressor, but the mechanism has been unclear. The p48 gene is required for expression of an ultraviolet radiation-damaged DNA binding activity and is disrupted by mutations in the subset of xeroderma pigmentosum group E cells that lack this activity. Here, we show that p48 mRNA levels strongly depend on basal p53 expression and increase further after DNA damage in a p53-dependent manner. Furthermore, like p53^−/− cells, xeroderma pigmentosum group E cells are deficient in global genomic repair. These results identify p48 as the link between p53 and the nucleotide excision repair apparatus.

Footnotes

↵ † B.J.H. and J.M.F. contributed equally to the work.
↵ § To whom reprint requests should be addressed at: M211, Division of Oncology, Stanford University Medical Center, Stanford, CA 94305-5115. e-mail: chu{at}cmgm.stanford.edu.
ABBREVIATIONS:

CPD,

cyclobutane pyrimidine dimer;

GGR,

global genomic repair;

IR,

ionizing radiation;

TCR,

transcription-coupled repair;

UV,

ultraviolet radiation;

UV-DDB,

UV-damaged DNA binding activity;

XP,

xeroderma pigmentosum