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Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I‐DNA covalent complex
Author(s) -
Horibata Katsuyoshi,
Saijo Masafumi,
Bay Mui N.,
Lan Li,
Kuraoka Isao,
Brooks Philip J.,
Honma Masamitsu,
Nohmi Takehiko,
Yasui Akira,
Tanaka Kiyoji
Publication year - 2011
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2010.01467.x
Subject(s) - biology , cockayne syndrome , microbiology and biotechnology , dna repair , dna , topoisomerase , mutant , transposable element , nucleotide excision repair , genetics , dna damage , gene
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.