Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I-DNA covalent complex

Genes Cells. 2011 Jan;16(1):101-14. doi: 10.1111/j.1365-2443.2010.01467.x. Epub 2010 Dec 9.


Two UV-sensitive syndrome patients who have mild photosensitivity without detectable somatic abnormalities lack detectable Cockayne syndrome group B (CSB) protein because of a homozygous null mutation in the CSB gene. In contrast, mutant CSB proteins are produced in CS-B patients with the severe somatic abnormalities of Cockayne syndrome and photosensitivity. It is known that the piggyBac transposable element derived 3 is integrated within the CSB intron 5, and that CSB-piggyBac transposable element derived 3 fusion (CPFP) mRNA is produced by alternative splicing. We found that CPFP or truncated CSB protein derived from CPFP mRNA was stably produced in CS-B patients, and that wild-type CSB, CPFP, and truncated CSB protein interacted with DNA topoisomerase I. We also found that CPFP inhibited repair of a camptothecin-induced topoisomerase I-DNA covalent complex. The inhibition was suppressed by the presence of wild-type CSB, consistent with the autosomal recessive inheritance of Cockayne syndrome. These results suggested that reduced repair of a DNA topoisomerase I-DNA covalent complex because of truncated CSB proteins is involved in the pathogenesis of CS-B.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Transformed
  • DNA / genetics
  • DNA / metabolism
  • DNA Repair / genetics*
  • DNA Repair Enzymes / physiology*
  • DNA Topoisomerases, Type I / genetics
  • DNA Topoisomerases, Type I / metabolism*
  • Fibroblasts / radiation effects
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Introns
  • Mutant Proteins / genetics*
  • Mutation
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Messenger / genetics
  • Transfection
  • Ultraviolet Rays


  • Mutant Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Messenger
  • DNA
  • Ercc6 protein, mouse
  • DNA Topoisomerases, Type I
  • TOP1 protein, human
  • DNA Repair Enzymes