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Molecular and Cellular Biology, February 2008, p. 988-996, Vol. 28, No. 3
0270-7306/08/$08.00+0 doi:10.1128/MCB.01366-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Enrico Cundari,1
Paola Ballario,1,2 and
Patrizia Filetici1*
Istituto di Biologia e Patologia Molecolari, CNR,1 Dip. Genetica e Biologia Molecolare, Sapienza Università di Roma, P. le A. Moro 5, 00185 Rome, Italy2
Received 30 July 2007/ Returned for modification 31 August 2007/ Accepted 5 November 2007
We report that the histone acetyltransferase Gcn5p is involved in cell cycle progression, whereas its absence induces several mitotic defects, including inefficient nuclear division, chromosome loss, delayed G2 progression, and spindle elongation. The fidelity of chromosome segregation is finely regulated by the close interplay between the centromere and the kinetochore, a protein complex hierarchically assembled in the centromeric DNA region, while disruption of GCN5 in mutants of inner components results in sick phenotype. These synthetic interactions involving the ADA complex lay the genetic basis for the critical role of Gcn5p in kinetochore assembly and function. We found that Gcn5p is, in fact, physically linked to the centromere, where it affects the structure of the variant centromeric nucleosome. Our findings offer a key insight into a Gcn5p-dependent epigenetic regulation at centromere/kinetochore in mitosis.
Published ahead of print on 26 November 2007.
Present address: Universität Tübingen Frauenklinink UKT, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
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