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Molecular and Cellular Biology, November 2002, p. 7907-7918, Vol. 22, No. 22
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.22.7907-7918.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Stimulation of DNA Replication from the Polyomavirus Origin by PCAF and GCN5 Acetyltransferases: Acetylation of Large T Antigen

An-Yong Xie,{dagger} Vladimir P. Bermudez,{ddagger} and William R. Folk*

Department of Biochemistry, University of Missouri—Columbia, Columbia, Missouri 65211

Received 15 May 2002/ Returned for modification 16 July 2002/ Accepted 15 August 2002

The PCAF and GCN5 acetyltransferases, but not p300 or CBP, stimulate DNA replication when tethered near the polyomavirus origin. Replication stimulation by PCAF and GCN5 is blocked by mutational inactivation of their acetyltransferase domains but not by deletion of sequences that bind p300 or CBP. Acetylation of histones near the polyomavirus origin assembled into chromatin in vivo is not detectably altered by expression of these acetyltransferases. PCAF and GCN5 interact with polyomavirus large T antigen in vivo, PCAF acetylates large T antigen in vitro, and large T-antigen acetylation in vivo is dependent upon the integrity of the PCAF acetyltransferase domain. These data suggest replication stimulation occurs through recruitment of large T antigen to the origin and acetylation by PCAF or GCN5.

* Corresponding author. Mailing address: 117 Schweitzer Hall, University of Missouri—Columbia, Columbia, MO 65211. Phone: (573) 882-2841. Fax: (573) 884-4812. E-mail: folkw{at}missouri.edu.

{dagger} Present address: Harvard Institute of Medicine, Beth Israel Dea-coness Medical Center, Boston, MA 02215.

{ddagger} Present address: Program in Molecular Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10021.

Molecular and Cellular Biology, November 2002, p. 7907-7918, Vol. 22, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.22.7907-7918.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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