Topoisomerase IB: a relaxing enzyme for stressed DNA

Abstract

DNA topoisomerase I enzymes relieve the torsional strain in DNA; they are essential for fundamental molecular processes such as DNA replication, transcription, recombination, and chromosome condensation; and act by cleaving and then religating DNA strands. Over the past few decades, scientists have focused on the DNA topoisomerases biological functions and established a unique role of Type I DNA topoisomerases in regulating gene expression and DNA chromosome condensation. Moreover, the human enzyme is being investigated as a target for cancer chemotherapy. The active site tyrosine is responsible for initiating two transesterification reactions to cleave and then religate the DNA backbone, allowing the release of superhelical tension. The different steps of the catalytic mechanism are affected by various inhibitors; some of them prevent the interaction between the enzyme and the DNA while others act as poisons, leading to TopI-DNA lesions, breakage of DNA, and eventually cellular death. In this review, our goal is to provide an overview of mechanism of human topoisomerase IB action together with the different types of inhibitors and their effect on the enzyme functionality.

Keywords

Human DNA topoisomerase IB / mechanism of action / drugs inhibition

References

[1] Nitiss JL.Investigating the biological functions of DNA topoisomerases in eukaryotic cells..Biochim Biophys Acta1998;1400:63-81

[2] Wang JC.Cellular roles of DNA topoisomerases: a molecular perspective..Nat Rev Mol Cell Biol2002;3:430-40

[3] Nakasu S.Reverse gyrase; ATP-dependent Type I topoisomerase from Sulfolobus..EMBO J1985;4:2705-10 PMCID:PMC554563

[4] Tse-Dinh YC.Bacterial and archeal Type I topoisomerases..Biochim Biophys Acta1998;1400:19-27

[5] Seki T,Katada T.Isolation of a cDNA encoding mouse DNA topoisomerase III which is highly expressed at the mRNA level in the testis..Biochim Biophys Acta1998;1396:127-31

[6] Slesarev AI,Lake JA.Topoisomerase V from Methanopyrus kandleri..Methods Enzymol2001;334:179-92

[7] Liu LF.Supercoiling of the DNA template during transcription..Proc Natl Acad Sci U S A1987;84:7024-7 PMCID:PMC299221

[8] Sissi C.Effects of magnesium and related divalent metal ions in topoisomerase structure and function..Nucleic Acids Res2009;37:702-11 PMCID:PMC2647314

[9] Cuya SM,van Waardenburg RCAM.DNA topoisomerase-targeting chemotherapeutics: what’s new?.Cancer Chemother Pharmacol2017;80:1-14

[10] Sekiguchi J.Site-specific ribonuclease activity of eukaryotic DNA topoisomerase I..Mol Cell1997;1:89-97

[11] Champoux JJ.DNA topoisomerases: structure, function, and mechanism..Annu Rev Biochem2001;70:369-413

[12] Pommier Y.Topoisomerase I inhibitors: camptothecins and beyond..Nat Rev Cancer2006;6:789-802

[13] Champoux JJ.Domains of human topoisomerase I and associated functions..Prog Nucleic Acid Res Mol Biol1998;60:111-32

[14] Stewart L,Champoux JJ.Reconstitution of human topoisomerase I by fragment complementation..J Mol Biol1997;269:355-72

[15] Redinbo MR,Champoux JJ.Structural flexibility in human topoisomerase I revealed in multiple non-isomorphous crystal structures..J Mol Biol1999;292:685-96

[16] Stewart L,Qiu X,Champoux JJ.A model for the mechanism of human topoisomerase I..Science1998;279:1534-41

[17] Wang Z,Tesauro C,Ottaviani A.Mutation of Gly717Phe in human topoisomerase 1B has an effect on enzymatic function, reactivity to the camptothecin anticancer drug and on the linker domain orientation..Biochim Biophys Acta2015;1854:860-8

[18] Stewart L,Champoux JJ.The domain organization of human topoisomerase I..J Biol Chem1996;271:7602-8

[19] Redinbo MR,Kuhn P,Hol WG.Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA..Science1998;279:1504-13

[20] Redinbo MR,Hol WG.Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA..Biochemistry2000;39:6832-40

[21] Laco GS.Role of a tryptophan anchor in human topoisomerase I structure, function and inhibition..Biochem J2008;411:523-30 PMCID:PMC2692499

[22] Albor A,Kulesz-Martin M.Wild-type and mutant forms of p53 activate human topoisomerase I: a possible mechanism for gain of function in mutants..Cancer Res1998;58:2091-4

[23] Bharti AK,Kufe DW.Identification of a nucleolin binding site in human topoisomerase I..J Biol Chem1996;271:1993-7

[24] Simmons DT,Usher D.Simian virus 40 large T antigen binds to topoisomerase..Virology1996;222:365-74

[25] Madden KR,Champoux JJ.Preferential binding of human topoisomerase I to superhelical DNA..EMBO J1995;14:5399-409 PMCID:PMC394649

[26] Schoeffler AJ.DNA topoisomerases: harnessing and constraining energy to govern chromosome topology..Q Rev Biophys2008;41:41-101

[27] Woo MH,Guo H,Benedetti P.Locking the DNA topoisomerase I protein clamp inhibits DNA rotation and induces cell lethality..Proc Natl Acad Sci U S A2003;100:13767-72 PMCID:PMC283496

[28] Coletta A.Role of the protein in the DNA sequence specificity of the cleavage site stabilized by the camptothecin topoisomerase IB inhibitor: a metadynamics study..Nucleic Acids Res2013;41:9977-86 PMCID:PMC3905883

[29] Siu FM.Sequence selectivity of the cleavage sites induced by topoisomerase I inhibitors: a molecular dynamics study..Nucleic Acids Res2013;41:10010-9 PMCID:PMC3905861

[30] Tesauro C,Ottaviani A,Zuccaro L.Molecular mechanism of the camptothecin resistance of Glu710Gly topoisomerase IB mutant analyzed in vitro and in silico..Mol Cancer2013;12:100 PMCID:PMC3766703

[31] D’Annessa I,Sutthibutpong T,Chillemi G.Simulations of DNA topoisomerase 1B bound to supercoiled DNA reveal changes in the flexibility pattern of the enzyme and a secondary protein-DNA binding site..Nucleic Acids Res2014;42:9304-12 PMCID:PMC4132758

[32] Sari L.Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxation..Nucleic Acids Res2005;33:6621-34 PMCID:PMC1298917

[33] Punchihewa C,Carver M.Human topoisomerase I C-terminal domain fragment containing the active site tyrosine is a molten globule: implication for the formation of competent productive complex..J Struct Biol2007;159:111-21 PMCID:PMC1993844

[34] Cretaio E,Fontebasso Y,Losasso C.Human DNA topoisomerase IB: structure and functions..Ital J Biochem2007;56:91-102

[35] Pettersen EF,Huang CC,Greenblatt DM.UCSF Chimera - a visualization system for exploratory research and analysis..J Comput Chem2004;25:1605-12

[36] Tesauro C,D’Annessa I,Turchi G.Erybraedin C, a natural compound from the plant Bituminaria bituminosa, inhibits both the cleavage and religation activities of human topoisomerase I..Biochem J2010;425:531-9

[37] Arnò B,Tesauro C,Fiorani P.A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism..Biosci Rep2013;33:e00025 PMCID:PMC3590572

[38] Wu N,Agama K,Du J.A novel DNA topoisomerase I inhibitor with different mechanism from camptothecin induces G2/M phase cell cycle arrest to K562 cells..Biochemistry2010;49:10131-6 PMCID:PMC3010555

[39] Ganguly A,Roy A,Dasgupta SB.Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death..Cancer Res2007;67:11848-58

[40] Beretta GL,Perego P.Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug..Curr Med Chem2013;20:1541-65

[41] Li F,Li Q.Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: Did we miss something in CPT analogue molecular targets for treating human disease such as cancer?.Am J Cancer Res2017;7:2350-94 PMCID:PMC5752681

[42] Pizzolato JF.Irinotecan (Campto®) in the treatment of pancreatic cancer..Expert Rev Anticancer Ther2003;3:587-93

[43] Pizzolato JF.The camptothecins..Lancet2003;361:2235-42

[44] Horwitz MS.Intracellular degradation of HeLa and adenovirus type 2 DNA induced by camptothecin..Biochem Biophys Res Commun1971;45:723-7

[45] Urasaki Y,Pourquier P,Kohlhagen G.Characterization of a novel topoisomerase I mutation from a camptothecin-resistant human prostate cancer cell line..Cancer Res2001;61:1964-9

[46] Pommier Y.DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition..Chem Rev2009;109:2894-902 PMCID:PMC2707511

[47] Lisby M,Skouboe C,Straub T.Residues within the N-terminal domain of human topoisomerase I play a direct role in relaxation..J Biol Chem2001;276:20220-7

[48] Fiorani P,Losasso C,Desideri A.The different cleavage DNA sequence specificity explains the camptothecin resistance of the human topoisomerase I Glu418Lys mutant..Nucleic Acids Res2006;34:5093-100 PMCID:PMC1636438

[49] Chrencik JE,Burgin AB,Pommier Y.Mechanisms of camptothecin resistance by human topoisomerase I mutations..J Mol Biol2004;339:773-84

[50] Benedetti P,Capuani L.Camptothecin resistance from a single mutation changing glycine 363 of human DNA topoisomerase I to cysteine..Cancer Res1993;53:4343-8

[51] Fiorani P,Silvestri A,Bjornsti MA.Domain interactions affecting human DNA topoisomerase I catalysis and camptothecin sensitivity..Mol Pharmacol1999;56:1105-15

[52] D’Annessa I,Wang Z,Zuccaro L.The human topoisomerase 1B Arg634Ala mutation results in camptothecin resistance and loss of inter-domain motion correlation..Biochim Biophys Acta2013;1834:2712-21

[53] D’Annessa I,Fiorani P,Castelli S.Role of flexibility in protein-DNA-drug recognition: the case of Asp677Gly-Val703Ile topoisomerase mutant hypersensitive to camptothecin..J Amino Acids2012;2012:206083 PMCID:PMC3270393

[54] Arnò B,Tesauro C,Ottaviani A.Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant..PLoS One2013;8:e68404 PMCID:PMC3699648

[55] Wright CM,DeBrot AH.DNA topoisomerase I domain interactions impact enzyme activity and sensitivity to camptothecin..J Biol Chem2015;290:12068-78 PMCID:PMC4424343

[56] Losasso C,Fiorani P,Chillemi G.A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance..Nucleic Acids Res2008;36:5635-44 PMCID:PMC2553582

[57] Pourquier P.Topoisomerase I-mediated DNA damage..Adv Cancer Res2001;80:189-216

[58] Fujimori A,Kohlhagen G,Pommier Y.Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin..Cancer Res1995;55:1339-46