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Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300.


Hasan, S; Stucki, M; Hassa, P O; Imhof, R; Gehrig, P; Hunziker, P; Hübscher, U; Hottiger, M O (2001). Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300. Molecular Cell, 7(6):1221-1231.

Abstract

We describe a role for the transcriptional coactivator p300 in DNA metabolism. p300 formed a complex with flap endonuclease-1 (Fen1) and acetylated Fen1 in vitro. Furthermore, Fen1 acetylation was observed in vivo and was enhanced upon UV treatment of human cells. Remarkably, acetylation of the Fen1 C terminus by p300 significantly reduced Fen1's DNA binding and nuclease activity. Proliferating cell nuclear antigen (PCNA) was able to stimulate both acetylated and unacetylated Fen1 activity to the same extent. Our results identify acetylation as a novel regulatory modification of Fen1 and implicate that p300 is not only a component of the chromatin remodeling machinery but might also play a critical role in regulating DNA metabolic events.

We describe a role for the transcriptional coactivator p300 in DNA metabolism. p300 formed a complex with flap endonuclease-1 (Fen1) and acetylated Fen1 in vitro. Furthermore, Fen1 acetylation was observed in vivo and was enhanced upon UV treatment of human cells. Remarkably, acetylation of the Fen1 C terminus by p300 significantly reduced Fen1's DNA binding and nuclease activity. Proliferating cell nuclear antigen (PCNA) was able to stimulate both acetylated and unacetylated Fen1 activity to the same extent. Our results identify acetylation as a novel regulatory modification of Fen1 and implicate that p300 is not only a component of the chromatin remodeling machinery but might also play a critical role in regulating DNA metabolic events.

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96 citations in Web of Science®
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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Biochemistry and Molecular Biology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1 June 2001
Deposited On:11 Feb 2008 12:18
Last Modified:05 Apr 2016 12:16
Publisher:Elsevier
ISSN:1097-2765
Publisher DOI:10.1016/S1097-2765(01)00272-6
PubMed ID:11430825

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