The novel human gene aprataxin is directly involved in DNA single-strand-break repair

Cell Mol Life Sci. 2005 Feb;62(4):485-91. doi: 10.1007/s00018-004-4441-0.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apraxia, Ideomotor / diagnosis
  • Apraxia, Ideomotor / genetics*
  • Camptothecin / pharmacology
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / genetics
  • Chromosome Aberrations
  • Comet Assay
  • DNA Damage* / genetics
  • DNA Repair* / genetics
  • DNA Topoisomerases, Type I / drug effects
  • DNA Topoisomerases, Type I / physiology
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Diagnosis, Differential
  • Humans
  • Male
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Pedigree
  • Point Mutation / genetics
  • Radiation Tolerance / genetics
  • X-Rays


  • APTX protein, human
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Nuclear Proteins
  • DNA Topoisomerases, Type I
  • Camptothecin