DNA topoisomerase I domain interactions impact enzyme activity and sensitivity to camptothecin.

The Journal of Biological Chemistry
Christine M WrightM A Bjornsti

Abstract

During processes such as DNA replication and transcription, DNA topoisomerase I (Top1) catalyzes the relaxation of DNA supercoils. The nuclear enzyme is also the cellular target of camptothecin (CPT) chemotherapeutics. Top1 contains four domains: the highly conserved core and C-terminal domains involved in catalysis, a coiled-coil linker domain of variable length, and a poorly conserved N-terminal domain. Yeast and human Top1 share a common reaction mechanism and domain structure. However, the human Top1 is ∼100-fold more sensitive to CPT. Moreover, substitutions of a conserved Gly(717) residue, which alter intrinsic enzyme sensitivity to CPT, induce distinct phenotypes in yeast. To address the structural basis for these differences, reciprocal swaps of yeast and human Top1 domains were engineered in chimeric enzymes. Here we report that intrinsic Top1 sensitivity to CPT is dictated by the composition of the conserved core and C-terminal domains. However, independent of CPT, biochemically similar chimeric enzymes produced strikingly distinct phenotypes in yeast. Expression of a human Top1 chimera containing the yeast linker domain proved toxic, even in the context of a catalytically inactive Y723F enzyme. Lethality was suppress...Continue Reading

References

Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M A Bjornsti, J C Wang
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·P D'ArpaW C Earnshaw
Jan 26, 1996·The Journal of Biological Chemistry·A K BhartiE H Rubin
Mar 29, 1996·The Journal of Biological Chemistry·L StewartJ J Champoux
May 9, 1997·The Journal of Biological Chemistry·M D MegonigalM A Bjornsti
Jun 13, 1997·Journal of Molecular Biology·L StewartJ J Champoux
Mar 21, 1998·Science·L StewartJ J Champoux
Oct 8, 1998·Advances in Enzyme Regulation·P Haluska, E H Rubin
Jul 27, 2000·Molecular Cell·B O Krogh, S Shuman
Aug 31, 2000·Annual Review of Biochemistry·S S Patel, K M Picha
Apr 3, 2001·The Journal of Biological Chemistry·M LisbyB R Knudsen
Jun 8, 2001·Annual Review of Biochemistry·J J Champoux
Aug 30, 2001·Proceedings of the National Academy of Sciences of the United States of America·H ZhangY Pommier
Feb 7, 2002·Proceedings of the National Academy of Sciences of the United States of America·Berit Olsen Krogh, Stewart Shuman
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·James C Wang
Oct 26, 2002·Cancer Cell·Mary Ann Bjornsti
Nov 12, 2002·Proceedings of the National Academy of Sciences of the United States of America·Bart L StakerLance Stewart
Nov 22, 2002·The Journal of Biological Chemistry·Héctor VillaDavid Ordóñez
Apr 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·James F CareyJames J Champoux
Oct 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Michael H WooMary-Ann Bjornsti
Jan 27, 2004·Journal of Molecular Biology·Rikke From FrøhlichBirgitta Ruth Knudsen
May 14, 2004·Annual Review of Biophysics and Biomolecular Structure·Kevin D Corbett, James M Berger
May 29, 2004·Journal of Molecular Biology·Jill E ChrencikMatthew R Redinbo
Oct 19, 2004·The Journal of Biological Chemistry·William C ColleyMary-Ann Bjornsti
Apr 26, 2005·Biochimica Et Biophysica Acta·Alicja CzubatyKrzysztof Staroń
Jun 15, 2005·Annual Review of Biochemistry·Aaron Johnson, Mike O'Donnell
Jun 20, 2006·Molecular and Cellular Biology·Robert C A M van WaardenburgMary-Ann Bjornsti
Jun 26, 2007·Nature·Daniel A KosterNynke H Dekker
Nov 29, 2007·Molecular Cell·Jacob G JansenNiels de Wind
Dec 7, 2007·Biochemical and Biophysical Research Communications·Agnieszka GirstunKrzysztof Staroń
Dec 7, 2007·The Journal of Biological Chemistry·Marié van der Merwe, Mary-Ann Bjornsti
Jan 15, 2008·Cell·Roxana E GeorgescuMike O'Donnell
Jan 25, 2008·The Biochemical Journal·Gary S Laco, Yves Pommier
Jun 11, 2010·Chemistry & Biology·Yves PommierChristophe Marchand
May 31, 2011·Molecular Cancer·Céline GongoraMaguy Del Rio
Nov 24, 2011·Nature Reviews. Molecular Cell Biology·Seychelle M VosJames M Berger
Mar 19, 2013·Annual Review of Biochemistry·Stefanie Hartman ChenTao-shih Hsieh

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Jul 19, 2016·Journal of Cellular Biochemistry·Agnieszka GirstunKrzysztof Staron
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