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 metaboli sm, p300 formed a complex with flap endonuclease-1 (Fen1) and acetylated Fe n1 in vitro. Furthermore, Fen1 acetylation was observed in vivo and was enh anced upon UV treatment of human cells. Remarkably, acetylation of the Fen1 C terminus by p300 significantly reduced Fen1's DNA binding and nuclease a ctivity. Proliferating cell nuclear antigen (PCNA) was able to stimulate bo th acetylated and unacetylated Fen1 activity to the same extent. Our result s identify acetylation as a novel regulatory modification of Fen1 and impli cate that p300 is not only a component of the chromatin remodeling machiner y but might also play a critical role in regulating DNA metabolic events.