PMID: 6408486Jul 7, 1983Paper

Inhibitor evidence for allosteric interaction in the replitase multienzyme complex

Nature
G P veer Reddy, A B Pardee

Abstract

We have previously shown that a fraction from the nuclei of S phase (DNA-synthesizing) Chinese hamster embryo fibroblasts (CHEF/18 cells) can be obtained that has a number of the enzyme activities required for DNA biosynthesis, and can catalyse the incorporation of labelled precursors into DNA (refs 1-4, also see ref. 8). This fraction, which we have termed the 'replitase', contains spherical particles of diameter approximately 25 nm, apparently multienzyme complexes for de novo DNA biosynthesis. Here we present evidence for the functional association of one of the enzyme activities, thymidylate synthase, with several of the other enzyme activities. Hydroxyurea, novobiocin and aphidicolin, inhibitors of ribonucleotide reductase, topoisomerase and DNA polymerase alpha, respectively, all inhibit thymidylate synthase in intact S phase CHEF/18 cells, but not in their soluble extracts. We suggest that these results reflect allosteric interactions between the subunits of a multienzyme DNA-synthesizing complex, which can be modulated by the specific inhibitors of individual enzyme activities in intact cells.

References

Jan 1, 1978·Advances in Enzyme Regulation·C K MathewsG Prem veer Reddy
Jul 29, 1971·Biochimica Et Biophysica Acta·R L AdamsA Thomson
Jun 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·G Prem veer Reddy, A B Pardee
Dec 15, 1982·Biochemical and Biophysical Research Communications·G Prem veer Reddy

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Citations

Dec 1, 1991·Journal of Cellular Biochemistry·R H GetzenbergD S Coffey
Nov 30, 1983·Biochemical and Biophysical Research Communications·R J Boorstein, A B Pardee
Feb 1, 1985·Biochemical Pharmacology·G B FitzGerald, M M Wick
Jul 1, 1988·Mutation Research·E T Snow, S Mitra
Jan 1, 1987·Advances in Enzyme Regulation·J G Cory
Jan 1, 1984·Pharmacology & Therapeutics·L M Nutter, Y C Cheng
Oct 5, 1984·Biochimica Et Biophysica Acta·V S Mikhailov, I M Androsova
Apr 16, 1998·Pharmacology & Therapeutics·W R Montfort, A Weichsel
May 3, 2002·Molecular Microbiology·Elena C GuzmánAlfonso Jiménez-Sánchez
Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·R W HonessR E Randall
Jan 30, 2010·The Journal of Biological Chemistry·Sahn-Ho KimG Prem-Veer Reddy
Oct 1, 1984·The Journal of Cell Biology·P K Gupta, M A Sirover
Apr 25, 1986·Nucleic Acids Research·P A DijkwelJ Poddighe
May 1, 1987·Antimicrobial Agents and Chemotherapy·A ForsgrenT F Tedder
May 1, 1987·The Journal of Clinical Investigation·J P EderL E Schnipper
Aug 6, 2009·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·J Scott BrockenbroughHubert Vesselle
Sep 27, 2006·Journal of Cellular Physiology·Shalini Murthy, G Prem-Veer Reddy
Apr 1, 1984·Bioscience Reports·D C Creasey, J A Wright
Sep 17, 1984·Biochemical and Biophysical Research Communications·P ChibaJ G Cory
Jun 16, 1987·Biochemistry·P Reichard
Aug 22, 2018·Annual Review of Nutrition·Martha S FieldPatrick J Stover
Jun 19, 1991·International Journal of Cancer. Journal International Du Cancer·J TanakaE Frei
Nov 7, 1998·The Journal of Biological Chemistry·P HatzisI Talianidis
Jun 27, 1997·The Journal of Biological Chemistry·V BianchiP Reichard
Jun 1, 1991·Molecular and Cellular Biology·T StokkeH B Steen
Feb 1, 1986·Experimental Cell Research·C K Mathews, M B Slabaugh

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