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J. Biol. Chem., Vol. 277, Issue 23, 20974-20978, June 7, 2002
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From the Department of Pharmacology and Therapeutics, McGill
University, 3655 Drummond Street, Montreal, Quebec H3G 1Y6,
Canada
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 study, we test the hypothesis that histone deacetylase 1 (HDAC1) 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
the HDAC inhibitor trichostatin A. Trichostatin A 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 after 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.
Proliferating Cell Nuclear Antigen Associates with
Histone Deacetylase Activity, Integrating DNA Replication and
Chromatin Modification*
,
*
This work was supported in part by the Canadian Institute of
Health Research.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by Philip Baily McGill Majors Fellowship.
§
To whom correspondence should be addressed. Tel.: 514-398-7107;
Fax: 514-398-6690; E-mail: mszyf@pharma.mcgill.ca.
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