Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome

Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15410-5. doi: 10.1073/pnas.0404587101. Epub 2004 Oct 14.


UV-sensitive syndrome (UVsS) is a rare autosomal recessive disorder characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors. UVsS cells show UV hypersensitivity and defective transcription-coupled DNA repair of UV damage. It was suggested that UVsS does not belong to any complementation groups of known photosensitive disorders such as xeroderma pigmentosum and Cockayne syndrome (CS). To identify the gene responsible for UVsS, we performed a microcell-mediated chromosome transfer based on the functional complementation of UV hypersensitivity. We found that one of the UVsS cell lines, UVs1KO, acquired UV resistance when human chromosome 10 was transferred. Because the gene responsible for CS group B (CSB), which involves neurological abnormalities and photosensitivity as well as a defect in transcription-coupled DNA repair of UV damage, is located on chromosome 10, we sequenced the CSB gene from UVs1KO and detected a homozygous null mutation. Our results indicate that previous complementation analysis of UVs1KO was erroneous. This finding was surprising because a null mutation of the CSB gene would be expected to result in CS features such as severe developmental and neurological abnormalities. On the other hand, no mutation in the CSB cDNA and a normal amount of CSB protein was detected in Kps3, a UVsS cell line obtained from an unrelated patient, indicating genetic heterogeneity in UVsS. Possible explanations for the discrepancy in the genotype-phenotype relationship in UVs1KO are presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosomes, Human, Pair 10
  • Cockayne Syndrome / etiology*
  • Cockayne Syndrome / genetics
  • DNA Helicases / genetics
  • DNA Helicases / physiology*
  • DNA Primers
  • DNA Repair
  • DNA Repair Enzymes
  • Fluorescent Antibody Technique
  • Genetic Complementation Test
  • Humans
  • Poly-ADP-Ribose Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA Primers
  • Poly-ADP-Ribose Binding Proteins
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes