Cellular roles of DNA topoisomerases: a molecular perspective

  title={Cellular roles of DNA topoisomerases: a molecular perspective},
  author={James C. Wang},
  journal={Nature Reviews Molecular Cell Biology},
  • James C. Wang
  • Published 1 June 2002
  • Biology, Chemistry
  • Nature Reviews Molecular Cell Biology
DNA topoisomerases are the magicians of the DNA world — by allowing DNA strands or double helices to pass through each other, they can solve all of the topological problems of DNA in replication, transcription and other cellular transactions. Extensive biochemical and structural studies over the past three decades have provided molecular models of how the various subfamilies of DNA topoisomerase manipulate DNA. In this review, the cellular roles of these enzymes are examined from a molecular… 
DNA topoisomerases and their functions in a cell
The review discusses the basic features of different types of topoisomerases with respect to the catalytic mechanism and focuses on the involvement of top Loisomerases in various DNA-related cell processes, such as replication, transcription, recombination, chromatin condensation, and daughter chromatid partitioning.
Introduction: emerging themes in DNA topoisomerase research.
A selection of the new themes that have been recently introduced into the already large body of topoisomerase research are discussed.
Cellular resistance to DNA Topoisomerase I-targeting drugs
Eukaryotic DNA topoisomerase I (top1) is a nuclear enzyme that releases the torsional stress of DNA resulting from various genetic processes including replication, recombination and transcription.
New mechanistic and functional insights into DNA topoisomerases.
Recent advances in mechanistic insights into topoisomerases are covered, including a DNA helicase capable of modulating the directionality of strand passage, enabling important functions like reannealing denatured DNA and resolving recombination intermediates.
Structure and mechanism of action of type IA DNA topoisomerases
This review summarizes the literature on type IA DNA topoisomerases and special attention is given to particular properties of their structure and mechanisms of functioning of these enzymes.
The many lives of type IA topoisomerases
This research interest is driven by a realization that DNA topoisomerases' substrate versatility and their ability to engage in intimate collaborations with translocases and other DNA-processing enzymes are far more extensive and impressive than was thought hitherto.
Structure and Mechanism of Eukaryotic Type IIA Topoisomerases
A wealth of biochemical and structural data on Top2 (topo II), the eukaryotic member of this topoisomerase family, as well as complementary studies on its bacterial counterparts (DNA gyrase and topo IV), has helped explain many essential features of this complex catalytic cycle.
Transcriptional functions of DNA Topoisomerases at a genome-wide scale and a single gene levels
The research project of the present thesis has been focused on the role of human TOP 1 during transcription and on the transcriptional consequences associated with TOP 1 inhibition by CPT in human cell lines, and suggest that TOP 1inhibition by C PT may increase the activity of Cdks which in turn phosphorylate the Rpb1 subunit of RNAP II enhancing its escape from pausing.
DNA Topoisomerases as Targets for the Chemotherapeutic Treatment of Cancer
This article will familiarize the reader with many aspects of topoisomerase enzymology and cell biology, their interactions with anticancer drugs, and the cellular consequences of topisomerase-mediated DNA strand breaks.
Human DNA Topoisomerase I: Structure, Enzymology and Biology
The list of proteins known to interact with human topoisomerase I suggests that the enzyme has functions in vivo that extend well beyond the previously characterized roles in replication, transcription, and chromatin assembly.


Investigating the biological functions of DNA topoisomerases in eukaryotic cells.
  • J. Nitiss
  • Biology
    Biochimica et biophysica acta
  • 1998
Structure and mechanism of DNA topoisomerase II
The crystal structure of a large fragment of yeast type II DNA topoisomerase reveals a heart-shaped dimeric protein with a large central hole. It provides a molecular model of the enzyme as an
DNA topoisomerases: structure, function, and mechanism.
Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the typeIIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes.
Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA.
The crystal structures of reconstituted human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps" around essentially B-form DNA.
DNA topoisomerases: why so many?
  • J. Wang
  • Biology, Medicine
    The Journal of biological chemistry
  • 1991
Several new DNA topoisomerases have been discovered recently. In the yeast Saccharomyces cereuisiae, a gene has been identified to encode a protein homologous to eubacterial DNA topoisomerase I; this
Function of DNA topoisomerases as replication swivels in Saccharomyces cerevisiae.
Molecular mechanisms of durg inhibition of DNA gyrase
Details of the mechanisms of inhibition for some classes of drugs have been established unequivocally by X‐ray crystallography, and it is hoped that this detailed structural information will assist the design of novel, effective inhibitors of DNA gyrase.
RecQ helicases and topoisomerases: components of a conserved complex for the regulation of genetic recombination
Recent biochemical and genetic evidence is reviewed to indicate that RecQ helicases or topoisomerases act in concert in a conserved pathway to maintain genomic stability by preventing inappropriate recombination.
Three-dimensional structure of the 67K N-terminal fragment of E. coli DNA topoisomerase I
The three-dimensional structure of the 67K amino-terminal fragment of E. coli DNA topoisomerase I suggests a plausible mechanism by which the organism could catalyse the passage of one DNA strand through a transient break in another strand.
Resolution of Holliday junctions by eukaryotic DNA topoisomerase I.
It is demonstrated that the vaccinia virus DNA topoisomerase, a eukaryotic type I enzyme, catalyzes resolution of synthetic Holliday junctions in vitro, suggesting a model whereby type I topoisomersases may either promote or suppress genetic recombination in vivo.