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Molecular and Cellular Biology, October 2000, p. 7643-7653, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
ATP-Dependent Chromatin Remodeling by the Cockayne Syndrome B DNA
Repair-Transcription-Coupling Factor
Elisabetta
Citterio,1
Vincent
Van Den Boom,1
Gavin
Schnitzler,2,
Roland
Kanaar,1,3
Edgar
Bonte,1
Robert E.
Kingston,2
Jan H. J.
Hoeijmakers,1,* and
Wim
Vermeulen1
Medical Genetic Center, Department of Cell
Biology and Genetics, Center for Biomedical Genetics, Erasmus
University Rotterdam, 3000 DR Rotterdam,1 and
Department of Radiation Oncology, Daniël den Hoed Cancer
Center, Rotterdam,3 The Netherlands, and
Department of Molecular Biology, Massachusetts General
Hospital, Boston, Massachusetts 021142
Received 28 February 2000/Returned for modification 5 April
2000/Accepted 24 July 2000
The Cockayne syndrome B protein (CSB) is required for coupling DNA
excision repair to transcription in a process known as transcription-coupled repair (TCR). Cockayne syndrome patients show UV
sensitivity and severe neurodevelopmental abnormalities. CSB is a
DNA-dependent ATPase of the SWI2/SNF2 family. SWI2/SNF2-like proteins
are implicated in chromatin remodeling during transcription. Since
chromatin structure also affects DNA repair efficiency, chromatin
remodeling activities within repair are expected. Here we used purified
recombinant CSB protein to investigate whether it can remodel chromatin
in vitro. We show that binding of CSB to DNA results in an alteration
of the DNA double-helix conformation. In addition, we find that CSB is
able to remodel chromatin structure at the expense of ATP hydrolysis.
Specifically, CSB can alter DNase I accessibility to reconstituted
mononucleosome cores and disarrange an array of nucleosomes regularly
spaced on plasmid DNA. In addition, we show that CSB interacts not only
with double-stranded DNA but also directly with core histones. Finally,
intact histone tails play an important role in CSB remodeling. CSB is
the first repair protein found to play a direct role in modulating
nucleosome structure. The relevance of this finding to the interplay
between transcription and repair is discussed.
*
Corresponding author. Mailing address: MGC
Dept. of
Cell Biology and Genetics, CBG, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31 10 408 7199. Fax:
31 10 408 9468. E-mail: hoeijmakers{at}gen.fgg.eur.nl.

Present address: Department of Biochemistry, Tufts University
School of Medicine, Boston, MA
02111.
Molecular and Cellular Biology, October 2000, p. 7643-7653, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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