Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Amino Acid Sequence
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Cell Line
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DNA Damage
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DNA Polymerase iota
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DNA Repair
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DNA Replication*
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DNA, Complementary
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DNA-Directed DNA Polymerase / chemistry
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DNA-Directed DNA Polymerase / genetics*
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DNA-Directed DNA Polymerase / physiology
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Frameshift Mutation
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Humans
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Molecular Sequence Data
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Mutation*
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Neoplasms, Radiation-Induced
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Protein Biosynthesis
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Pyrimidine Dimers / metabolism
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Saccharomyces cerevisiae / genetics
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Sequence Alignment
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Sequence Deletion
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Skin Neoplasms / etiology
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Ultraviolet Rays
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Xeroderma Pigmentosum / genetics*
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Xeroderma Pigmentosum / metabolism
Substances
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DNA, Complementary
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Pyrimidine Dimers
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DNA-Directed DNA Polymerase
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Rad30 protein
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DNA Polymerase iota