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The Cockayne syndrome group B protein is a functional dimer
Author(s) -
Christiansen Mette,
Thorslund Tina,
Jochimsen Bjarne,
Bohr Vilhelm A.,
Stevnsner Tinna
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04844.x
Subject(s) - cockayne syndrome , dimer , chromatin , atpase , protein quaternary structure , biology , dna , nucleotide excision repair , transcription (linguistics) , dna repair , biochemistry , microbiology and biotechnology , chemistry , protein subunit , gene , enzyme , linguistics , philosophy , organic chemistry
Cockayne syndrome (CS) is a rare inherited human genetic disorder characterized by developmental abnormalities, UV sensitivity, and premature aging. The CS group B (CSB) protein belongs to the SNF2‐family of DNA‐dependent ATPases and is implicated in transcription elongation, transcription coupled repair, and base excision repair. It is a DNA stimulated ATPase and remodels chromatin in vitro . We demonstrate for the first time that full‐length CSB positively cooperates in ATP hydrolysis as a function of protein concentration. We have investigated the quaternary structure of CSB using a combination of protein–protein complex trapping experiments and gel filtration, and found that CSB forms a dimer in solution. Chromatography studies revealed that enzymatically active CSB has an apparent molecular mass of approximately 360 kDa, consistent with dimerization of CSB. Importantly, in vivo protein cross‐linking showed the presence of the CSB dimer in the nucleus of HeLa cells. We further show that dimerization occurs through the central ATPase domain of the protein. These results have implications for the mechanism of action of CSB, and suggest that other SNF2‐family members might also function as dimers.