title: The novel human gene aprataxin is directly involved in DNA single-strand-break repair.
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.
authors.affiliation: Dipartimento di Agrobiologia e Agrochimica, Università degli Studi della Tuscia, Via San Camino de Lellis s.n.c., 01100 Viterbo, Italy. mosesso@unitus.it.
authors.forename: P
authors.initials: P
authors.lastname: Mosesso
authors.forename: M
authors.initials: M
authors.lastname: Piane
authors.forename: F
authors.initials: F
authors.lastname: Palitti
authors.forename: G
authors.initials: G
authors.lastname: Pepe
authors.forename: S
authors.initials: S
authors.lastname: Penna
authors.forename: L
authors.initials: L
authors.lastname: Chessa
mesh_terms: D020240:Apraxia, Ideomotor / Q000175:diagnosis / Q000235:genetics*; D002166:Camptothecin / Q000494:pharmacology; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000235:genetics; D002869:Chromosome Aberrations; D020552:Comet Assay; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000502:physiology; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D003937:Diagnosis, Differential; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D014965:X-Rays
chemical_list: C438188:APTX protein, human; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin
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