title: Misrepair of DNA double-strand breaks in patient with unidentified chromosomal fragility syndrome and family history of radiosensitivity.
abstract: OBJECTIVE
  To test the hypothesis that differences in DNA double-strand breaks (DSB) repair fidelity underlies differences in radiosensitivity.
  
  
  METHODS
  A primary fibroblast culture (C42) derived from a pediatric cancer patient treated with reduced radiation doses consequent to a family history of radiosensitivity reminiscent of chromosomal fragility syndrome, was compared to a normal control (C29). DNA DSB rejoining and repair fidelity were studied by Southern blotting and hybridization to specific fragments: Alu repetitive sequence representing the overall DSB rejoining capacity in the genome and a 3.2 Mbp NotI restriction fragment on chromosome 21 for DSB repair fidelity.
  
  
  RESULTS
  Although both assays showed statistically significant difference (p ≤ 0.05) between the two cell strains in residual misrepaired (un-or mis-rejoined) DSB (24 h after 30 or 80 Gy), the residual damage was lower in the Alu enriched genome assay compared to NotI assay (0.01-0.07 and 0.10-0.37, respectively).
  
  
  CONCLUSIONS
  These results suggest that, in comparison to classic DSB repair experiment, an assay of measuring DNA DSB repair fidelity can provide better resolution and a more accurate estimate of misrepair of radiation-induced DNA damage, which underlies genomic instability and increased radiosensitivity.
authors.affiliation: King Faisal Specialist Hospital & Research Centre , Riyadh , Saudi Arabia.
authors.forename: Ghazi
authors.initials: G
authors.lastname: Alsbeih
authors.forename: Williams
authors.initials: W
authors.lastname: Brock
authors.forename: Michael
authors.initials: M
authors.lastname: Story
mesh_terms: D020137:Base Pair Mismatch / Q000235:genetics / Q000528:radiation effects; D001681:Biological Assay / Q000379:methods; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics*; D002873:Chromosome Fragility / Q000235:genetics* / Q000528:radiation effects*; D004249:DNA Damage / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics* / Q000528:radiation effects*; D005260:Female; D006801:Humans; D011836:Radiation Tolerance / Q000235:genetics*