Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300.
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.
Hasan
S
S
Institute of Veterinary Biochemistry, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
Stucki
M
M
Hassa
P O
PO
Imhof
R
R
Gehrig
P
P
Hunziker
P
P
Hübscher
U
U
Hottiger
M O
MO
D000107:Acetylation / Q000528:radiation effects; D000595:Amino Acid Sequence; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D045585:Flap Endonucleases; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014466:Ultraviolet Rays
D002843:Chromatin; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D015534:Trans-Activators; D004247:DNA; D004706:Endodeoxyribonucleases; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D008239:Lysine