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

Katsuyoshi Horibata, Masafumi Saijo, Mui N. Bay, Li Lan, Isao Kuraoka, Philip J. Brooks, Masamitsu Honma, Takehiko Nohmi, Akira Yasui, Kiyoji Tanaka

    Research output: Contribution to journalArticlepeer-review

    19 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)101-114
    Number of pages14
    JournalGenes to Cells
    Volume16
    Issue number1
    DOIs
    Publication statusPublished - 2011 Jan

    ASJC Scopus subject areas

    • Genetics
    • Cell Biology

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