Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome

抄録

UV sensitive syndrome (UV^sS) is a rare autosomal recessive disorder characterized by solar sensitivity and freckling, but no neurological abnormality and skin tumors. It is known that UV^sS does not belong to any complementation groups of xeroderma pigmentosum (XP) or Cockayne syndrome (CS), and that UV^sS lacks an ability of transcription-coupled repair (TCR). This fact suggests that UV^sS belongs to a new category of photosensitive disorder with defective TCR. To identify the gene responsible for UV^sS cells, UV^s1KO, we have performed microcell-mediated chromosome transfer based on functional complementation of its high-UV sensitivity. We found that UV^s1KO cells acquired the UV-resistance when chromosome 10 was transferred. Since the CSB gene is located on chromosome 10, we sequenced the CSB cDNA. Surprisingly, the homozygous nonsense mutation was detected on the CSB cDNA in the UV^s1KO cells. These results indicated that UV^sS is caused by the mutation on the CSB gene. To confirm these results, we transfected the wild type CSB cDNA into UV^s1KO cells. The transfectants exhibited the same UV-resistant character as wild type cells. These data indicated that UV^sS is caused by the mutation of CSB gene in spite of the absence of any growth and neurological failure observed in CS-B patients.