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

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.

[1]  G. Chu,et al.  DNA-dependent protein kinase is not required for accumulation of p53 or cell cycle arrest after DNA damage. , 1997, Cancer research.

[2]  J. Wootton,et al.  A 127 kDa component of a UV-damaged DNA-binding complex, which is defective in some xeroderma pigmentosum group E patients, is homologous to a slime mold protein. , 1993, Nucleic acids research.

[3]  S. Keeney,et al.  Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Hanawalt,et al.  DNA repair in an active gene: Removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall , 1985, Cell.

[5]  P. Hanawalt,et al.  Transcript cleavage by RNA polymerase II arrested by a cyclobutane pyrimidine dimer in the DNA template. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[6]  P. J. van der Spek,et al.  Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. , 1998, Molecular cell.

[7]  S. Keeney,et al.  Comparative analysis of binding of human damaged DNA-binding protein (XPE) and Escherichia coli damage recognition protein (UvrA) to the major ultraviolet photoproducts: T[c,s]T, T[t,s]T, T[6-4]T, and T[Dewar]T. , 1993, The Journal of biological chemistry.

[8]  S. Keeney,et al.  Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein. , 1995, Genomics.

[9]  P. Hanawalt,et al.  Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene , 1987, Cell.

[10]  G. Wahl,et al.  Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles , 1992, Cell.

[11]  S. Elledge,et al.  The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases , 1993, Cell.

[12]  A. Levine,et al.  Purification of an ultraviolet-inducible, damage-specific DNA-binding protein from primate cells. , 1991, The Journal of biological chemistry.

[13]  I. Guénal,et al.  Down-regulation of actin genes precedes microfilament network disruption and actin cleavage during p53-mediated apoptosis. , 1997, Journal of cell science.

[14]  P. Hanawalt,et al.  Human fibroblasts expressing the human papillomavirus E6 gene are deficient in global genomic nucleotide excision repair and sensitive to ultraviolet irradiation. , 1998, Cancer research.

[15]  G. Chu,et al.  Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes explain the diseases? , 1996, Trends in genetics : TIG.

[16]  P. Hanawalt,et al.  Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in global DNA repair but exhibit normal transcription-coupled repair and enhanced UV resistance. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  P. O'Connor,et al.  Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. , 1994, Science.

[18]  R. Wood,et al.  Preferential binding of the xeroderma pigmentosum group A complementing protein to damaged DNA. , 1993, Biochemistry.

[19]  K. Kinzler,et al.  A model for p53-induced apoptosis , 1997, Nature.

[20]  p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity , 1998, Molecular and Cellular Biology.

[21]  A. Levine p53, the Cellular Gatekeeper for Growth and Division , 1997, Cell.

[22]  J. Trent,et al.  WAF1, a potential mediator of p53 tumor suppression , 1993, Cell.

[23]  Mammalian nucleotide excision repair and syndromes. , 1997, Biochemical Society transactions.

[24]  D. K. Treiber,et al.  An ultraviolet light-damaged DNA recognition protein absent in xeroderma pigmentosum group E cells binds selectively to pyrimidine (6-4) pyrimidone photoproducts. , 1992, Nucleic acids research.

[25]  P. Hanawalt Transcription-coupled repair and human disease. , 1994, Science.

[26]  G. Chu,et al.  Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. , 1988, Science.

[27]  M. Shahin The protective effect of 4-[(2-oxo-3-bornylidene)methyl]-phenyl trimethylammonium methylsulphate against the induction of gene mutations by ultraviolet, visible light and 8-methoxypsoralen in Saccharomyces cerevisiae. , 1992, Mutation research.

[28]  S. Keeney,et al.  Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E. , 1993, The Journal of biological chemistry.

[29]  R. Wood,et al.  Mammalian DNA nucleotide excision repair reconstituted with purified protein components , 1995, Cell.

[30]  Xin Lu,et al.  Differential induction of transcriptionally active p53 following UV or lonizing radiation: Defects in chromosome instability syndromes? , 1993, Cell.

[31]  P. Hanawalt,et al.  Expression of Wild-type p53 Is Required for Efficient Global Genomic Nucleotide Excision Repair in UV-irradiated Human Fibroblasts* , 1997, The Journal of Biological Chemistry.

[32]  P. Hanawalt,et al.  Excision-repair patch lengths are similar for transcription-coupled repair and global genome repair in UV-irradiated human cells. , 1997, Mutation research.

[33]  S. Linn,et al.  Mutations Specific to the Xeroderma Pigmentosum Group E Ddb− Phenotype* , 1996, The Journal of Biological Chemistry.

[34]  G. Chu,et al.  Purification and characterization of a human protein that binds to damaged DNA. , 1993, Biochemistry.

[35]  G. Chu,et al.  Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells. , 1996, Mutation research.