hRAD30 mutations in the variant form of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by a high incidence of skin cancers. Yeast RAD30 encodes a DNA polymerase involved in the error-free bypass of ultraviolet (UV) damage. Here it is shown that XP variant (XP-V) cell lines harbor nonsense or frameshift mutations in hRAD30, the human counterpart of yeast RAD30. Of the eight mutations identified, seven would result in a severely truncated hRad30 protein. These results indicate that defects in hRAD30 cause XP-V, and they suggest that error-free replication of UV lesions by hRad30 plays an important role in minimizing the incidence of sunlight-induced skin cancers.

[1]  Robert E. Johnson,et al.  Requirement of DNA Polymerase Activity of Yeast Rad30 Protein for Its Biological Function* , 1999, The Journal of Biological Chemistry.

[2]  Robert E. Johnson,et al.  Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta. , 1999, Science.

[3]  J. Vos,et al.  Defective bypass replication of a leading strand cyclobutane thymine dimer in xeroderma pigmentosum variant cell extracts. , 1998, Cancer research.

[4]  Errol C. Friedberg,et al.  Deletion of the Saccharomyces cerevisiae gene RAD30 encoding an Escherichia coli DinB homolog confers UV radiation sensitivity and altered mutability , 1998, Molecular and General Genetics MGG.

[5]  J P McDonald,et al.  Is Dna Damage Inducible and Functions in a Novel Error-free Postreplication Repair Mechanism , 1997 .

[6]  W. Kaufmann,et al.  Replication Fork Bypass of a Pyrimidine Dimer Blocking Leading Strand DNA Synthesis* , 1997, The Journal of Biological Chemistry.

[7]  C. Lawrence,et al.  Deoxycytidyl transferase activity of yeast REV1 protein , 1996, Nature.

[8]  W. Mcgregor,et al.  Comparison of the rate of excision of major UV photoproducts in the strands of the human HPRT gene of normal and xeroderma pigmentosum variant cells. , 1996, Mutation research.

[9]  A. Sancar.  DNA excision repair. , 1996, Annual review of biochemistry.

[10]  M. Seidman,et al.  Xeroderma pigmentosum and related disorders: examining the linkage between defective DNA repair and cancer. , 1994, The Journal of investigative dermatology.

[11]  H. L. Waters,et al.  Ultraviolet hypermutability of a shuttle vector propagated in xeroderma pigmentosum variant cells. , 1993, The Journal of investigative dermatology.

[12]  D. Mitchell,et al.  Evidence from mutation spectra that the UV hypermutability of xeroderma pigmentosum variant cells reflects abnormal, error-prone replication on a template containing photoproducts , 1993, Molecular and cellular biology.

[13]  W. Kaufmann,et al.  Defective postreplication repair in xeroderma pigmentosum variant fibroblasts. , 1990, Cancer research.

[14]  J. Cleaver,et al.  Xeroderma pigmentosum variants. , 1981, Cytogenetics and cell genetics.

[15]  W. Kaufmann,et al.  Similar defects in DNA repair and replication in the pigmented xerodermoid and the xeroderma pigmentosum variants. , 1980, Carcinogenesis.

[16]  M. Paterson,et al.  Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Cleaver,et al.  Xeroderma pigmentosum: variants with normal DNA repair and normal sensitivity to ultraviolet light. , 1972, The Journal of investigative dermatology.