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Papers In Press, published online ahead of print April 2, 2002
Department of Pharmacology, McGill University, Montreal, Quebec H3G 1Y6
Corresponding Author: mszyf{at}pharma.mcgill.ca
Faithful inheritance of the chromatin structure is essential for maintaining the gene expression integrity of a cell. Histone modification by acetylation and deacetylation is a critical control of chromatin structure. In this paper we test the hypothesis that histone deacetylase 1 (HDAC 1) is physically associated with a basic component of the DNA replication machinery as a mechanism of coordinating histone deacetylation and DNA synthesis. Proliferating cell nuclear antigen (PCNA) is a sliding clamp that serves as a loading platform for many proteins involved in DNA replication and DNA repair. We show that PCNA interacts with HDAC1 in human cells and in vitro, and that a considerable fraction of PCNA and HDAC1 colocalize in the cell nucleus. PCNA associates with histone deacetylase activity that is completely abolished in the presence of HDAC inhibitor Trichostatin A (TSA). TSA treatment arrests cells at the G2/M phase of the cell cycle which is consistent with the hypothesis that the proper formation of the chromatin following DNA replication may be important in signaling the progression through the cell cycle. Our results strengthen the role of PCNA as a factor coordinating DNA replication and epigenetic inheritance.
J. Biol. Chem, 10.1074/jbc.M202504200
Submitted on March 14, 2002
Revised on April 2, 2002
Accepted on April 1, 2002
PCNA associates with histone deacetylase activity, integrating DNA replication and chromatin modification
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