Abstract
Mutations in CSB gene give rise to two kinds of disorders. One is Cockayne syndrome (CS) group B showing photosensitivity, abnormalities in physical and neurological development, and another is UV-sensitive syndrome (UVsS) characterized by only mild photosensitivity without any abnormalities in physical and neurological development. One of the UVsS patients, UVs1KO, has no CSB protein due to homozygous null mutation in CSB gene, while various types of mutant CSB proteins are produced in CS-B cells. We have hypothesized that mutant CSB proteins produced in CS-B cells may have an inhibitory function, leading to CS-features. It is known that transposable element PGBD3 is integrated in the intron 5 of CSB gene. We found that the CSB-PGBD3 fusion mRNA is not targeted to nonsense-mediated mRNA decay even when 5'-terminal part of CSB has a nonsense mutation, resulting in the stable production of truncated CSB protein in CS-B cells. We also found that the wild type and truncated CSB proteins interacted with topoisomerase I (Top1), and the truncated CSB proteins inhibited catalytic cycle of Top1, implicating that the CS features are caused at least by an inhibition of catalytic cycle of Top1.
