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Biomedical subjects

S R Peterson

Publications and source records attributed to S R Peterson.

7 recordsLinked to original sources

Ku autoantigen is the regulatory component of a template-associated protein kinase that phosphorylates RNA polymerase II.

The carboxyl-terminal domain of RNA polymerase II contains a tandemly repeated heptapeptide sequence. Previous work has shown that this sequence is phosphorylated at multiple sites by a template-associated protein kinase, in a reaction that is closely associated with the initiation of RNA synthesis. We have purified this kinase to apparent homogeneity from human (HeLa) cells. The purified kinase phosphorylates native RNA polymerase II only in the presence of DNA and the general transcription factors TFIID (TBP), TFIIB, and TFIIF. Two kinase components are required for full activity: a catalytic component and a DNA-binding regulatory component. The regulatory component has been identified as Ku autoantigen, based on the molecular weights of its component polypeptides, its DNA-binding properties, and its reactivity with anti-Ku monoclonal antibodies. The Ku autoantigen recruits the catalytic component of the kinase to the template. Ku autoantigen has been previously proposed to interact with DNA by a characteristic bind-and-slide mechanism. This mode of interaction may provide a mechanism for targeting the kinase to the transcription complex and other DNA-bound substrates.

Antigens, Nuclear

DNA binding provides a signal for phosphorylation of the RNA polymerase II heptapeptide repeats.

Isolated transcription complexes contain a protein kinase that phosphorylates the heptapeptide repeats of the carboxy-terminal domain (CTD) of the RNA polymerase II (RNAP II) large subunit in an apparently promoter-dependent manner. We now show that the essential features of this reaction can be reproduced in a reconstituted system containing three macromolecular components: a fusion protein consisting of the CTD of RNAP II fused to a heterologous DNA-binding domain, an activating DNA fragment containing the recognition sequence for the fusion protein, and a protein kinase that binds nonspecifically to DNA. This kinase closely resembles a previously known DNA-dependent protein kinase. Evidently, the association of the CTD with DNA provides a key signal for phosphorylation. There appears to be no absolute requirement for specific contacts with other DNA-bound transcription factors.

Animals

Promoter-dependent phosphorylation of RNA polymerase II by a template-bound kinase. Association with transcriptional initiation.

The largest subunit of eukaryotic RNA polymerase II (RNAP II) has a serine- and threonine-rich C-terminal domain (CTD) that may interact both with DNA and with the activating region of transcription factors. It has been proposed, in one model, that a protein kinase phosphorylates the promoter-associated CTD, facilitating the transition between promoter-binding and RNA-elongating forms of RNAP II. An immobilized template transcription system was used to test the predictions of this model directly. A protein kinase that phosphorylated the CTD at multiple sites was detected. This activity was tightly bound to the template, as evidenced by continued association after multiple rounds of washing. Phosphorylation was promoter sequence-dependent and exhibited the same nucleotide substrate specificity as the previously characterized ATP-requiring step in initiation. It was necessary for [gamma-32P]ATP and initiating rNTPs to be present simultaneously in the reaction in order to efficiently chase-radiolabel into elongating RNAP II-containing complexes, consistent with the idea that initiation and phosphorylation are temporally associated reactions.

Adenosine Triphosphate

Evolution of a veterinary medical library.

Planning a new library and developing a book and journal collection for the College of Veterinary Medicine at Iowa State University are described. The Veterinary Medical Library is a self-contained unit (6,800 square feet) for print material within the Veterinary Medical Building. Seating for 140 patrons is available. The collection is designed to provide basic materials for teaching and research in veterinary and comparative medicine. Indexing and abstracting tools permit access to local, state, and national resources as well. At present the collection totals over 17,000 volumes and over 500 serial titles. A working collection of 25,000 volumes will be maintained in the Veterinary Medical Library, and the University Library will continue to function as the principal backup source.

Book Collecting

Hepatic dysfunction during hyperalimentation.

Liver biopsy specimens were studied in 26 patients in whom liver function abnormalities developed during intravenous hyperalimentation (IVH). The clinical manifestations and duration of IVH were evaluated in relation to the morphological changes seen in the liver. Early hepatic changes consisted of fatty metamorphosis, and progressive intrahepatic cholestasis developed as IVH was continued. Essential fatty acid deficiency, amino acid imbalance, caloric excess, and toxic manifestations of certain amino acids are postulated as causative factors. The hepatic steatosis secondary to IVH may be treated by lowering the dextrose concentration of the infusion or by administering dextrose-free amino acid solutions. The clinical importance of this common complication of IVH is the difficulty in distinguishing it from other causes of cholestasis in seriously ill patients.

Adult

p,p'-DDE, polychlorinated biphenyls, and endrin in oldsquaws in North America, 1969-73.

Organochlorinated compounds were monitored in oldsquaws (Clangula hyemalis) and their food from Lake Michigan between October and May, 1969-72; in adult oldsquaws, eggs, young, and food from northwest Hudson Bay in 1971; and in oldquaws from five wintering areas other than Lake Michigan in 1971-73. Analyses were conducted on 300 carcasses, 14 wings, 29 gullet samples, and 11 clutches. Average residues in carcasses from Lake Michigan ranged from 4 to 107 ppm PCBs, 2 to 42 ppm DDE, and less than 0.1 to 0.7 ppm endrin. Differences in DDE levels occurred between several sex and age classes during December on Lake Michigan; these differences were not apparent in the spring. Increases in DDE and PCB residues for oldsquaws occurred on Lake Michigan between December and May. DDE residues in the wing and carcass were significantly correlated. Residues were relatively low in oldsquaw foods from Lake Michigan; concentration factors between the food and the ducks varied between 1X and 22X, depending on the date and compound. Organochlorinated residues were lower in Arctic than in Lake Michigan food samples. DDE in paired male and female oldsquaws was highly correlated, as was DDE in females and clutches. Eggshell thickness had declined 4.5% compared with eggs collected before 1947. Residues were higher in oldsquaws wintering on the Great Lakes and lowest in oldsquaws from coastal areas.

Age Factors