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

Abstract

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.

• Authors: Katsuyoshi Horibata, Masafumi Saijo, Mui N Bay, Li Lan, Isao Kuraoka, Philip J Brooks, Masamitsu Honma, Takehiko Nohmi, Akira Yasui, Kiyoji Tanaka
• Journal: Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 16 Issue 1 Pg. 101-14 (Jan 2011) ISSN: 1365-2443 [Electronic] England
• PMID: 21143350 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Journal compilation © 2010 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

Chemical References

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

Topics

• Cell Line
• Cell Line, Transformed
• DNA (genetics, metabolism)
• DNA Repair (genetics)
• DNA Repair Enzymes (physiology)
• DNA Topoisomerases, Type I (genetics, 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