The Experts below are selected from a list of 68361 Experts worldwide ranked by ideXlab platform
Patrick Forterre - One of the best experts on this subject based on the ideXlab platform.
-
topib a phylogenetic hallmark gene of thaumarchaeota encodes a functional eukaryote like Topoisomerase ib
Nucleic Acids Research, 2016Co-Authors: Narimane Dahmane, Hongliang Zhang, Yves Pommier, Danièle Gadelle, Stephane Delmas, Alexis Criscuolo, Stephan Eberhard, Nicole Desnoues, Sylvie Collin, Patrick ForterreAbstract:Type IB DNA Topoisomerases can eliminate torsional stresses produced during replication and transcription. These enzymes are found in all eukaryotes and a short version is present in some bacteria and viruses. Among prokaryotes, the long eukaryotic version is only observed in archaea of the phylum Thaumarchaeota. However, the activities and the roles of these Topoisomerases have remained an open question. Here, we demonstrate that all available thaumarchaeal genomes contain a Topoisomerase IB gene that defines a monophyletic group closely related to the eukaryotic enzymes. We show that the topIB gene is expressed in the model thaumarchaeon Nitrososphaera viennensis and we purified the recombinant enzyme from the uncultivated thaumarchaeon Candidatus Caldiarchaeum subterraneum. This enzyme is active in vitro at high temperature, making it the first thermophilic Topoisomerase IB characterized so far. We have compared this archaeal type IB enzyme to its human mitochondrial and nuclear counterparts. The archaeal enzyme relaxes both negatively and positively supercoiled DNA like the eukaryotic enzymes. However, its pattern of DNA cleavage specificity is different and it is resistant to camptothecins (CPTs) and non-CPT Top1 inhibitors, LMP744 and lamellarin D. This newly described thermostable Topoisomerases IB should be a promising new model for evolutionary, mechanistic and structural studies.
-
DNA Topoisomerase VIII: a novel subfamily of type IIB Topoisomerases encoded by free or integrated plasmids in Archaea and Bacteria
Nucleic Acids Research, 2014Co-Authors: Danièle Gadelle, Mart Krupovic, Kasie Raymann, Claudine Mayer, Patrick ForterreAbstract:Type II DNA Topoisomerases are divided into two families, IIA and IIB. Types IIA and IIB enzymes share homologous B subunits encompassing the ATP-binding site, but have non-homologous A subunits catalyzing DNA cleavage. Type IIA Topoisomerases are ubiquitous in Bacteria and Eukarya, whereas members of the IIB family are mostly present in Archaea and plants. Here, we report the detection of genes encoding type IIB enzymes in which the A and B subunits are fused into a single polypeptide. These proteins are encoded in several bacterial genomes, two bacterial plasmids and one archaeal plasmid. They form a monophyletic group that is very divergent from archaeal and eukaryotic type IIB enzymes (DNA Topoisomerase VI). We propose to classify them into a new subfamily, denoted DNA Topoisomerase VIII. Bacterial genes encoding a Topoisomerase VIII are present within integrated mobile elements, most likely derived from conjugative plasmids. Purified Topoisomerase VIII encoded by the plasmid pPPM1a from Paenibacillus polymyxa M1 had ATP-dependent relaxation and decatenation activities. In contrast, the enzyme encoded by mobile elements integrated into the genome of Ammonifex degensii exhibited DNA cleavage activity producing a full-length linear plasmid and that from Microscilla marina exhibited ATP-independent relaxation activity. Topoisomerases VIII, the smallest known type IIB enzymes, could be new promising models for structural and mechanistic studies.
-
Origin and evolution of DNA Topoisomerases.
Biochimie, 2007Co-Authors: Patrick Forterre, Danièle Gadelle, Simonetta Gribaldo, Marie-claude SerreAbstract:The DNA Topoisomerases are essential for DNA replication, transcription, recombination, as well as for chromosome compaction and segregation. They may have appeared early during the formation of the modern DNA world. Several families and subfamilies of the two types of DNA Topoisomerases (I and II) have been described in the three cellular domains of life (Archaea, Bacteria and Eukarya), as well as in viruses infecting eukaryotes or bacteria. The main families of DNA Topoisomerases, Topo IA, Topo IB, Topo IC (Topo V), Topo IIA and Topo IIB (Topo VI) are not homologous, indicating that they originated independently. However, some of them share homologous modules or subunits that were probably recruited independently to produce different Topoisomerase activities. The puzzling phylogenetic distribution of the various DNA Topoisomerase families and subfamilies cannot be easily reconciled with the classical models of early evolution describing the relationships between the three cellular domains. A possible scenario is based on a Last Universal Common Ancestor (LUCA) with a RNA genome (i.e. without the need for DNA Topoisomerases). Different families of DNA Topoisomerases (some of them possibly of viral origin) would then have been independently introduced in the different cellular domains. We review here the main characteristics of the different families and subfamilies of DNA Topoisomerases in a historical and evolutionary perspective, with the hope to stimulate further works and discussions on the origin and evolution of these fascinating enzymes.
-
DNA Topoisomerase V: a new fold of mysterious origin
Trends in Biotechnology, 2006Co-Authors: Patrick ForterreAbstract:Although all other Topoisomerases have a broad phylogenetic distribution, DNA Topoisomerase V, the major component of the ThermoFidelase sequencing kit, is presently only known in a single species--the archaeon Methanopyrus kandleri. Resolution of the structure of this enzyme by Taneja and co-workers now reveals that this atypical Topoisomerase has no structural similarity with other proteins. So, where did it come from? It is my contention that Topo V, and many other orphan proteins, could have a viral origin.
Alexei I Slesarev - One of the best experts on this subject based on the ideXlab platform.
-
Topoisomerase v relaxes supercoiled dna by a constrained swiveling mechanism
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Bhupesh Taneja, Bernhard Schnurr, Alexei I Slesarev, John F Marko, Alfonso MondragonAbstract:Topoisomerase V is a type I Topoisomerase without structural or sequence similarities to other Topoisomerases. Although it belongs to the type I subfamily of Topoisomerases, it is unrelated to either type IA or IB enzymes. We used real-time single-molecule micromechanical experiments to show that Topoisomerase V relaxes DNA via events that release multiple DNA turns, employing a constrained swiveling mechanism similar to that for type IB enzymes. Relaxation is powered by the torque in the supercoiled DNA and is constrained by friction between the protein and the DNA. Although all type IB enzymes share a common structure and mechanism and type IA and type II enzymes show marked structural and functional similarities, Topoisomerase V represents a different type of Topoisomerase that relaxes DNA in a similar overall manner as type IB molecules but by using a completely different structural and mechanistic framework.
-
Structure of the N‐terminal fragment of Topoisomerase V reveals a new family of Topoisomerases
The EMBO Journal, 2006Co-Authors: Bhupesh Taneja, Alexei I Slesarev, Asmita Patel, Alfonso MondragonAbstract:Topoisomerases are involved in controlling and maintaining the topology of DNA and are present in all kingdoms of life. Unlike all other types of Topoisomerases, similar type IB enzymes have only been identified in bacteria and eukarya. The only putative type IB Topoisomerase in archaea is represented by Methanopyrus kandleri Topoisomerase V. Despite several common functional characteristics, Topoisomerase V shows no sequence similarity to other members of the same type. The structure of the 61 kDa N-terminal fragment of Topoisomerase V reveals no structural similarity to other Topoisomerases. Furthermore, the structure of the active site region is different, suggesting no conservation in the cleavage and religation mechanism. Additionally, the active site is buried, indicating the need of a conformational change for activity. The presence of a Topoisomerase in archaea with a unique structure suggests the evolution of a separate mechanism to alter DNA.
-
dna Topoisomerase v is a relative of eukaryotic Topoisomerase i from a hyperthermophilic prokaryote
Nature, 1993Co-Authors: Alexei I Slesarev, Karl O Stetter, James A Lake, Martin Gellert, Regis Krah, Sergei A KozyavkinAbstract:THE DNA Topoisomerases are ubiquitous enzymes that fulfil vital roles in the replication, transcription and recombination of DNA by carrying out DNA-strand passage reactions1–7. Here we characterize a prokaryotic counterpart to the eukaryotic Topoisomerase I in the hyperthermophilic methanogen Methanopyrus handleri8–10. The new enzyme, called Topoisomerase V, has the following properties in common with eukaryotic Topoisomerase I, which distinguish it from all other known prokaryotic Topoisomerases: (1) its activity is Mg2+-independent; (2) it relaxes both negatively and positively supercoiled DNA; (3) it makes a covalent complex with the 3' end of the broken DNA strand; and (4) it is recognized by antibody raised against human Topoisomerase I. Eukaryotic-like enzymes have been discovered in some hyperthermophilic prokaryotes, namely the eocytes11 and the extremely thermophilic archaebacteria12, and hyperthermophilic homologues of eukaryotic DNA polymerase-α, transcription factor IIB and DNA ligase13–15 have all been reported. Thus our findings support the idea that some essential parts of the eukaryotic transcription–translation and replication machineries were in place before the emergence of eukaryotes, and that the closest living relatives of eukaryotes may be hyperthermophiles.
-
dna Topoisomerase iii from extremely thermophilic archaebacteria atp independent type i Topoisomerase from desulfurococcus amylolyticus drives extensive unwinding of closed circular dna at high temperature
Journal of Biological Chemistry, 1991Co-Authors: Alexei I Slesarev, Karl O Stetter, D A Zaitzev, V M Kopylov, S A KozyavkinAbstract:Abstract A second type I Topoisomerase was purified from the extremely thermophilic archaebacterium Desulfurococcus amylolyticus. In contrast to the previously described reverse gyrase from this organism, the novel enzyme designated as Dam Topoisomerase III is an ATP-independent relaxing Topoisomerase. It is a monomer with Mr 108,000, as determined by electrophoresis under denaturing conditions and by size exclusion chromatography. Dam Topoisomerase III, like other bacterial type I Topoisomerases, absolutely requires Mg2+ for activity and is specific for single-stranded DNA. At 60-80 degrees C, it relaxes negatively but not positively supercoiled DNA and is inhibited by single-stranded M13 DNA. At 95 degrees C, the enzyme unwinds both positively and negatively supercoiled substrates and produces extensively unwound form I* and I** DNA. The peculiarities of DNA topoisomerization at high temperatures are discussed.
Yves Pommier - One of the best experts on this subject based on the ideXlab platform.
-
topib a phylogenetic hallmark gene of thaumarchaeota encodes a functional eukaryote like Topoisomerase ib
Nucleic Acids Research, 2016Co-Authors: Narimane Dahmane, Hongliang Zhang, Yves Pommier, Danièle Gadelle, Stephane Delmas, Alexis Criscuolo, Stephan Eberhard, Nicole Desnoues, Sylvie Collin, Patrick ForterreAbstract:Type IB DNA Topoisomerases can eliminate torsional stresses produced during replication and transcription. These enzymes are found in all eukaryotes and a short version is present in some bacteria and viruses. Among prokaryotes, the long eukaryotic version is only observed in archaea of the phylum Thaumarchaeota. However, the activities and the roles of these Topoisomerases have remained an open question. Here, we demonstrate that all available thaumarchaeal genomes contain a Topoisomerase IB gene that defines a monophyletic group closely related to the eukaryotic enzymes. We show that the topIB gene is expressed in the model thaumarchaeon Nitrososphaera viennensis and we purified the recombinant enzyme from the uncultivated thaumarchaeon Candidatus Caldiarchaeum subterraneum. This enzyme is active in vitro at high temperature, making it the first thermophilic Topoisomerase IB characterized so far. We have compared this archaeal type IB enzyme to its human mitochondrial and nuclear counterparts. The archaeal enzyme relaxes both negatively and positively supercoiled DNA like the eukaryotic enzymes. However, its pattern of DNA cleavage specificity is different and it is resistant to camptothecins (CPTs) and non-CPT Top1 inhibitors, LMP744 and lamellarin D. This newly described thermostable Topoisomerases IB should be a promising new model for evolutionary, mechanistic and structural studies.
-
Drugging Topoisomerases: Lessons and Challenges
ACS Chemical Biology, 2013Co-Authors: Yves PommierAbstract:Topoisomerases are ubiquitous enzymes that control DNA supercoiling and entanglements. They are essential during transcription and replication, and Topoisomerase inhibitors are among the most effective and most commonly used anticancer and antibacterial drugs. This review consists of two parts. In the first part (“Lessons”), it gives background information on the catalytic mechanisms of the different enzyme families (6 different genes in humans and 4 in most bacteria), describes the “interfacial inhibition” by which Topoisomerase-targeted drugs act as Topoisomerase poisons, and describes clinically relevant Topoisomerase inhibitors. It generalizes the interfacial inhibition principle, which was discovered from the mechanism of action of Topoisomerase inhibitors, and discusses how Topoisomerase inhibitors kill cells by trapping Topoisomerases on DNA rather than by classical enzymatic inhibition. Trapping protein–DNA complexes extends to a novel mechanism of action of PARP inhibitors and could be applied to...
-
DNA Topoisomerases and their poisoning by anticancer and antibacterial drugs.
Chemistry & Biology, 2010Co-Authors: Yves Pommier, Hongliang Zhang, Elisabetta Leo, Christophe MarchandAbstract:DNA Topoisomerases are the targets of important anticancer and antibacterial drugs. Camptothecins and novel noncamptothecins in clinical development (indenoisoquinolines and ARC-111) target eukaryotic type IB Topoisomerases (Top1), whereas human type IIA Topoisomerases (Top2α and Top2β) are the targets of the widely used anticancer agents etoposide, anthracyclines (doxorubicin, daunorubicin), and mitoxantrone. Bacterial type II Topoisomerases (gyrase and Topo IV) are the targets of quinolones and aminocoumarin antibiotics. This review focuses on the molecular and biochemical characteristics of Topoisomerases and their inhibitors. We also discuss the common mechanism of action of Topoisomerase poisons by interfacial inhibition and trapping of Topoisomerase cleavage complexes.
-
importance of the fourth alpha helix within the cap homology domain of type ii Topoisomerase for dna cleavage site recognition and quinolone action
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: D Strumberg, John L. Nitiss, Jiaowang Dong, Jerrylaine Walker, Marc C Nicklaus, Kurt W Kohn, Jonathan G Heddle, Anthony Maxwell, Siegfried Seeber, Yves PommierAbstract:We report that point mutations causing alteration of the fourth alpha-helix (α4-helix) of the CAP homology domain of eukaryotic (Saccharomyces cerevisiae) type II Topoisomerases (Ser740Trp, Gln743Pro, and Thr744Pro) change the selection of type II Topoisomerase-mediated DNA cleavage sites promoted by Ca2+ or produced by etoposide, the fluoroquinolone CP-115,953, or mitoxantrone. By contrast, Thr744Ala substitution had minimal effect on Ca2+- and drug-stimulated DNA cleavage sites, indicating the selectivity of single amino acid substitutions within the α4-helix on type II Topoisomerase-mediated DNA cleavage. The equivalent mutation in the gene for Escherichia coli gyrase causing Ser83Trp also changed the DNA cleavage pattern generated by Ca2+ or quinolones. Finally, Thr744Pro substitution in the yeast type II Topoisomerase rendered the enzyme sensitive to antibacterial quinolones. This study shows that the α4-helix within the conserved CAP homology domain of type II Topoisomerases is critical for selecting the sites of DNA cleavage. It also demonstrates that selective amino acid residues in the α4-helix are important in determining the activity and possibly the binding of quinolones to the Topoisomerase II-DNA complexes.
-
Topoisomerase I-mediated DNA damage
2001Co-Authors: Philippe Pourquier, Yves PommierAbstract:Topoisomerase I is a ubiquitous and essential enzyme in multicellular organisms. It is involved in multiple DNA transactions including DNA replication, transcription, chromosome condensation and decondensation, and probably DNA recombination. Besides its activity of DNA relaxation necessary to eliminate torsional stresses associated with these processes, Topoisomerase I may have other functions related to its interaction with other cellular proteins. Topoisomerase I is the target of the novel anticancer drugs, the camptothecins. Recently a broad range of physiological and environmentally-induced DNA modifications have also been shown to poison Topoisomerases. This review summarizes the various factors that enhance or suppress top1 cleavage complexes and discusses the significance of such effects. We also review the different mechanisms that have been proposed for the repair of Topoisomerase I-mediated DNA lesions.
Anthony Maxwell - One of the best experts on this subject based on the ideXlab platform.
-
how do type ii Topoisomerases use atp hydrolysis to simplify dna topology beyond equilibrium investigating the relaxation reaction of nonsupercoiling type ii Topoisomerases
Journal of Molecular Biology, 2009Co-Authors: Tanya Stuchinskaya, Kevin D. Corbett, James M. Berger, Lesley A Mitchenall, Allyn J Schoeffler, Andrew D Bates, Anthony MaxwellAbstract:Abstract DNA Topoisomerases control the topology of DNA (e.g., the level of supercoiling) in all cells. Type IIA Topoisomerases are ATP-dependent enzymes that have been shown to simplify the topology of their DNA substrates to a level beyond that expected at equilibrium (i.e., more relaxed than the product of relaxation by ATP-independent enzymes, such as type I Topoisomerases, or a lower-than-equilibrium level of catenation). The mechanism of this effect is currently unknown, although several models have been suggested. We have analyzed the DNA relaxation reactions of type II Topoisomerases to further explore this phenomenon. We find that all type IIA Topoisomerases tested exhibit the effect to a similar degree and that it is not dependent on the supercoil-sensing C-terminal domains of the enzymes. As recently reported, the type IIB Topoisomerase, Topoisomerase VI (which is only distantly related to type IIA enzymes), does not exhibit topology simplification. We find that topology simplification is not significantly dependent on circle size in the range ∼ 2–9 kbp and is not altered by reducing the free energy available from ATP hydrolysis by varying the ADP:ATP ratio. A direct test of one model (DNA tracking; i.e., sliding of a protein clamp along DNA to trap supercoils) suggests that this is unlikely to be the explanation for the effect. We conclude that geometric selection of DNA segments by the enzymes is likely to be a primary source of the effect, but that it is possible that other kinetic factors contribute. We also speculate whether topology simplification might simply be an evolutionary relic, with no adaptive significance.
-
importance of the fourth alpha helix within the cap homology domain of type ii Topoisomerase for dna cleavage site recognition and quinolone action
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: D Strumberg, John L. Nitiss, Jiaowang Dong, Jerrylaine Walker, Marc C Nicklaus, Kurt W Kohn, Jonathan G Heddle, Anthony Maxwell, Siegfried Seeber, Yves PommierAbstract:We report that point mutations causing alteration of the fourth alpha-helix (α4-helix) of the CAP homology domain of eukaryotic (Saccharomyces cerevisiae) type II Topoisomerases (Ser740Trp, Gln743Pro, and Thr744Pro) change the selection of type II Topoisomerase-mediated DNA cleavage sites promoted by Ca2+ or produced by etoposide, the fluoroquinolone CP-115,953, or mitoxantrone. By contrast, Thr744Ala substitution had minimal effect on Ca2+- and drug-stimulated DNA cleavage sites, indicating the selectivity of single amino acid substitutions within the α4-helix on type II Topoisomerase-mediated DNA cleavage. The equivalent mutation in the gene for Escherichia coli gyrase causing Ser83Trp also changed the DNA cleavage pattern generated by Ca2+ or quinolones. Finally, Thr744Pro substitution in the yeast type II Topoisomerase rendered the enzyme sensitive to antibacterial quinolones. This study shows that the α4-helix within the conserved CAP homology domain of type II Topoisomerases is critical for selecting the sites of DNA cleavage. It also demonstrates that selective amino acid residues in the α4-helix are important in determining the activity and possibly the binding of quinolones to the Topoisomerase II-DNA complexes.
Sergei A Kozyavkin - One of the best experts on this subject based on the ideXlab platform.
-
dna Topoisomerase v is a relative of eukaryotic Topoisomerase i from a hyperthermophilic prokaryote
Nature, 1993Co-Authors: Alexei I Slesarev, Karl O Stetter, James A Lake, Martin Gellert, Regis Krah, Sergei A KozyavkinAbstract:THE DNA Topoisomerases are ubiquitous enzymes that fulfil vital roles in the replication, transcription and recombination of DNA by carrying out DNA-strand passage reactions1–7. Here we characterize a prokaryotic counterpart to the eukaryotic Topoisomerase I in the hyperthermophilic methanogen Methanopyrus handleri8–10. The new enzyme, called Topoisomerase V, has the following properties in common with eukaryotic Topoisomerase I, which distinguish it from all other known prokaryotic Topoisomerases: (1) its activity is Mg2+-independent; (2) it relaxes both negatively and positively supercoiled DNA; (3) it makes a covalent complex with the 3' end of the broken DNA strand; and (4) it is recognized by antibody raised against human Topoisomerase I. Eukaryotic-like enzymes have been discovered in some hyperthermophilic prokaryotes, namely the eocytes11 and the extremely thermophilic archaebacteria12, and hyperthermophilic homologues of eukaryotic DNA polymerase-α, transcription factor IIB and DNA ligase13–15 have all been reported. Thus our findings support the idea that some essential parts of the eukaryotic transcription–translation and replication machineries were in place before the emergence of eukaryotes, and that the closest living relatives of eukaryotes may be hyperthermophiles.
