Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I-DNA covalent complex.
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.
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Related Subject Headings
- Ultraviolet Rays
- Transfection
- RNA, Messenger
- Poly-ADP-Ribose Binding Proteins
- Mutation
- Mutant Proteins
- Introns
- Humans
- HEK293 Cells
- Gene Knockdown Techniques
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ultraviolet Rays
- Transfection
- RNA, Messenger
- Poly-ADP-Ribose Binding Proteins
- Mutation
- Mutant Proteins
- Introns
- Humans
- HEK293 Cells
- Gene Knockdown Techniques