Abstract
The cells of an ataxia-oculomotor apraxia type 1 (AOA1) patient, homozygous for a new aprataxin mutation (T739C), were treated with camptothecin, an inhibitor of DNA topoisomerase I which induces DNA single-strand breaks. DNA damage was evaluated by cytogenetic analysis of chromosomal aberrations. The results obtained showed marked and dose-related increases in induced chromosomal aberrations in the patient and her heterozygous mother compared to the intrafamilial wild-type control. The alkaline comet assay confirmed this pattern. Moreover, the AOA1 cells did not show hypersensitivity to ionizing radiation, i.e. X-rays. These findings clearly indicate the direct involvement of aprataxin in the DNA single-strand-break repair machinery.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apraxia, Ideomotor / diagnosis
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Apraxia, Ideomotor / genetics*
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Camptothecin / pharmacology
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Cerebellar Ataxia / diagnosis
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Cerebellar Ataxia / genetics
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Chromosome Aberrations
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Comet Assay
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DNA Damage* / genetics
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DNA Repair* / genetics
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DNA Topoisomerases, Type I / drug effects
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DNA Topoisomerases, Type I / physiology
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DNA, Single-Stranded / metabolism
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Diagnosis, Differential
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Humans
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Male
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Nuclear Proteins / analysis
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Pedigree
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Point Mutation / genetics
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Radiation Tolerance / genetics
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X-Rays
Substances
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APTX protein, human
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DNA, Single-Stranded
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DNA-Binding Proteins
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Nuclear Proteins
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DNA Topoisomerases, Type I
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Camptothecin