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Originally published in Science Express on 11 October 2001
Science 21 December 2001:
Vol. 294. no. 5551, pp. 2539 - 2542
DOI: 10.1126/science.1064027

Reports

Requirement of Heterochromatin for Cohesion at Centromeres

Pascal Bernard,1* Jean-François Maure,2* Janet F. Partridge,1 Sylvie Genier,2 Jean-Paul Javerzat,2 Robin C. Allshire1dagger

Centromeres are heterochromatic in many organisms, but the mitotic function of this silent chromatin remains unknown. During cell division, newly replicated sister chromatids must cohere until anaphase when Scc1/Rad21-mediated cohesion is destroyed. In metazoans, chromosome arm cohesins dissociate during prophase, leaving centromeres as the only linkage before anaphase. It is not known what distinguishes centromere cohesion from arm cohesion. Fission yeast Swi6 (a Heterochromatin protein 1 counterpart) is a component of silent heterochromatin. Here we show that this heterochromatin is specifically required for cohesion between sister centromeres. Swi6 is required for association of Rad21-cohesin with centromeres but not along chromosome arms and, thus, acts to distinguish centromere from arm cohesion. Therefore, one function of centromeric heterochromatin is to attract cohesin, thereby ensuring sister centromere cohesion and proper chromosome segregation.

1 MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
2 Institut de Biochimie et Génétique Cellulaires, CNRS, Unité Mixte de Recherche 5095, 1 Rue Camille Saint Saëns, 33077 Bordeaux Cedex, France.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: robin.allshire{at}hgu.mrc.ac.uk


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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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R. Festenstein, S. N. Pagakis, K. Hiragami, D. Lyon, A. Verreault, B. Sekkali, and D. Kioussis (2003)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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P. Provost, R. A. Silverstein, D. Dishart, J. Walfridsson, I. Djupedal, B. Kniola, A. Wright, B. Samuelsson, O. Radmark, and K. Ekwall (2002)
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   Abstract »    Full Text »    PDF »
Two Ubiquitin-Conjugating Enzymes, Rhp6 and UbcX, Regulate Heterochromatin Silencing in Schizosaccharomyces pombe.
E. S. Choi, H. S. Kim, Y. K. Jang, S. H. Hong, and S. D. Park (2002)
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   Abstract »    Full Text »    PDF »
Cell-cycle control of the establishment of mating-type silencing in S. cerevisiae.
A. Lau, H. Blitzblau, and S. P. Bell (2002)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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