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T. M. Michaelidis, I. Grummt

Mechanism of Inhibition of RNA Polymerase I Transcription by DNA-dependent Protein Kinase

DNAdependent protein kinase represses RNA polymerase I (Pol I) transcription in vitro. To investigate the mechanism underlying transcriptional repression, we compared Pol I transcription in extracts from cells that either contain or lack the catalytic subunit of DNAPK (DNAPKcs). ATPdependent repression of Pol I transcription was observed in extracts from DNAPKcscontaining but not deficient cells, required templates with free DNA ends, and was overcome by exogenous SL1, the factor that nucleates initiation complex formation. Orderofaddition experiments demonstrate that DNAPKcs does not inactivate component(s) of the PolI transcription machinery. Instead, phosphorylated Ku protein competes with SL1 for binding to the rDNA promoter and, as a consequence, prevents initiation complex formation. The results reveal a novel mechanism of transcriptional regulation by DNAPK. Once targeted to DNA, autophosphorylated Ku may displace positive or negativeacting factors from their target sites, thereby repressing or activating transcription in a genespecific manner.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 383, 11/2002
Pages: 1683 - 1690

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