Mechanism of Inhibition of RNA Polymerase I Transcription by DNA-dependent Protein Kinase
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T. M. Michaelidis
Abstract
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.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Pigment Epithelium-Derived Factor (PEDF), a Serpin with Potent Anti-Angiogenic and Neurite Outgrowth-promoting Properties
- Mechanism of Inhibition of RNA Polymerase I Transcription by DNA-dependent Protein Kinase
- Evidence for Haploinsufficiency of the Human HNF1α Gene Revealed by Functional Characterization of MODY3-Associated Mutations
- In vitro and in vivo Stability of the 2ζ2 Protein Complex of the Broad Host-Range Streptococcus pyogenes pSM19035 Addiction System
- Effects of Antineoplastic Agents on Cytoplasmic and Membrane-Bound Heat Shock Protein 70 (Hsp70) Levels
- Characterization of the VPS10 Domain of SorLA/LR11 as Binding Site for the Neuropeptide HA
- Substrate Specificity and Inhibitor Studies of a Membrane-Bound Ganglioside Sialidase Isolated from Human Brain Tissue
- Specificity Determinants in the Interaction of Apolipoprotein(a) Kringles with Tetranectin and LDL
- Amylin-Induced Cytotoxicity Is Associated with Activation of Caspase-3 and MAP Kinases
- 2-Alkyl-3-Alkylamino-2H-Benzo- and Pyridothiadiazine 1,1-Dioxides: From K+ATP Channel Openers to Ca++ Channel Blockers?
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- Molecular Cloning and Chimerisation of an Inhibitory Anti-Cathepsin B Antibody and Its Expression in Chinese Hamster Ovary Cells
- Application of Peptides Containing the Cleavage Sequence of Pro-TNFα in Assessing TACE Activity of Whole Cells
