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Volume 270, Number 10, Issue of March 10, 1995 pp. 5289-5298
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
E2F-1 and a Cyclin-like DNA Repair Enzyme, Uracil-DNA Glycosylase, Provide Evidence for an Autoregulatory Mechanism for Transcription

(Received for publication, October 19, 1994; and in revised form, December 16, 1994)

Martin J. Walsh ,  Gongliang Shue,  Kathy Spidoni ,  Ajoy Kapoor

The cell cycle-dependent transcription factor, E2F-1, regulates the cyclin-like species of the DNA repair enzyme uracil-DNA glycosylase (UDG) gene in human osteosarcoma (Saos-2) cells. We demonstrate, through the deletion of the human UDG promoter sequences, that expression of E2F-1 activates the UDG promoter through several E2F sites. The major putative downstream site for E2F, located in the first exon, serves as a target for E2F-1/DP1 complex binding in vitro. We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F. High levels of UDG expression in a transient transfection assay result in the down-regulation of transcriptional activity through elements specific for E2F-mediated transcription. Overexpression of UDG in Saos 2 cells was observed to delay growth late in G(1) phase and transiently arrest these cells from progressing into the S phase. This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription, likely through E2F. This implicates E2F as a multifunctional target for proteins and enzymes, possibly, responsive to DNA damage through the negative effect of UDG on E2F-mediated transcriptional activity.



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Copyright © 1995 by the American Society for Biochemistry and Molecular Biology.