Edwards T K, Saleem A, Shaman J A, Dennis T, Gerigk C, Oliveros E, Gartenberg M R, Rubin E H
Departments of Medicine/Pharmacology, Cancer Institute of New Jersey/Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08901, USA.
J Biol Chem. 2000 Nov 17;275(46):36181-8. doi: 10.1074/jbc.M006628200.
Nucleolin functions in ribosome biogenesis and contains an acidic N terminus that binds nuclear localization sequences. In previous work we showed that human nucleolin associates with the N-terminal region of human topoisomerase I (Top1). We have now mapped the topoisomerase I interaction domain of nucleolin to the N-terminal 225 amino acids. We also show that the Saccharomyces cerevisiae nucleolin ortholog, Nsr1p, physically interacts with yeast topoisomerase I, yTop1p. Studies of isogenic NSR1(+) and Deltansr1 strains indicate that NSR1 is important in determining the cellular localization of yTop1p. Moreover, deletion of NSR1 reduces sensitivity to camptothecin, an antineoplastic topoisomerase I inhibitor. By contrast, Deltansr1 cells are hypersensitive to the topoisomerase II-targeting drug amsacrine. These findings indicate that nucleolin/Nsr1 is involved in the cellular localization of Top1 and that this localization may be important in determining sensitivity to drugs that target topoisomerases.
