Abstract
Structure-specific recognition proteins (SSRPs) bind to DNA containing intrastrand cross-links formed by the anticancer drug cisplatin. A yeast gene encoding an SSRP, designated IXR1, was cloned and sequenced. The Ixr1 protein, a member of the high mobility group-box protein family, bound specifically to DNA modified with cisplatin but not inactive platinum compounds. A yeast strain with an inactivated IXR1 gene was half as sensitive to cisplatin and accumulated one-third as many platinum-DNA lesions after treatment with cisplatin as the parental strain. These findings suggest that SSRPs play a role in mediating the cytotoxicity of cisplatin.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Cisplatin / metabolism*
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Cisplatin / pharmacology*
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Cloning, Molecular
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DNA / metabolism*
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DNA Adducts*
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DNA, Fungal / metabolism*
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DNA-Binding Proteins*
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Fungal Proteins / chemistry
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Genes, Fungal
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High Mobility Group Proteins / chemistry
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High Mobility Group Proteins / genetics
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High Mobility Group Proteins / metabolism*
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Molecular Sequence Data
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Saccharomyces cerevisiae / chemistry
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins*
Substances
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DNA Adducts
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DNA, Fungal
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DNA-Binding Proteins
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Fungal Proteins
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High Mobility Group Proteins
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IXR1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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cisplatin-DNA adduct
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DNA
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Cisplatin