scholarly journals Hindering the Strand Passage Reaction of Human Topoisomerase IIα without Disturbing DNA Cleavage, ATP Hydrolysis, or the Operation of the N-terminal Clamp

2004 ◽  
Vol 279 (27) ◽  
pp. 28093-28099 ◽  
Author(s):  
Vibe H. Oestergaard ◽  
Laura Giangiacomo ◽  
Lotte Bjergbaek ◽  
Birgitta R. Knudsen ◽  
Anni H. Andersen
Keyword(s):  
Dna Cleavage ◽  
Atp Hydrolysis ◽  
Topoisomerase Iiα ◽  
Strand Passage

scholarly journals CryoEM structures of open dimers of Gyrase A in complex with DNA illuminate mechanism of strand passage

2018 ◽  
Author(s):  
Katarzyna M. Soczek ◽  
Tim Grant ◽  
Peter B. Rosenthal ◽  
Alfonso Mondragon
Keyword(s):  
Conformational Changes ◽  
Dna Cleavage ◽  
Atp Hydrolysis ◽  
Unique Type ◽  
Dna Molecule ◽  
Gyrase A ◽  
A Subunit ◽  
Important Intermediate ◽  
Dna Strand ◽  
Strand Passage

AbstractGyrase is a unique type IIA topoisomerase that uses ATP hydrolysis to maintain the negatively supercoiled state of bacterial DNA. In order to perform its function, gyrase undergoes a sequence of conformational changes that consist of concerted gate openings, DNA cleavage, and DNA strand passage events. Structures where the transported DNA molecule (T-segment) is trapped by the A subunit have not been observed. Here we present the cryoEM structures of two oligomeric complexes of open gyrase A dimers and DNA. The protein subunits in these complexes were solved to 4 Å and 5.16 Å resolution. One of the complexes traps a linear DNA molecule, a putative T-segment, which interacts with the open gyrase A dimers in two states, representing steps either prior to or after passage through the DNA-gate. The structures locate the T-segment in important intermediate conformations of the catalytic cycle and provide insights into gyrase-DNA interactions and mechanism.

scholarly journals CryoEM structures of open dimers of gyrase A in complex with DNA illuminate mechanism of strand passage

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Katarzyna M Soczek ◽  
Tim Grant ◽  
Peter B Rosenthal ◽  
Alfonso Mondragón
Keyword(s):  
Conformational Changes ◽  
Dna Cleavage ◽  
Atp Hydrolysis ◽  
Unique Type ◽  
Dna Molecule ◽  
Gyrase A ◽  
A Subunit ◽  
Important Intermediate ◽  
Dna Strand ◽  
Strand Passage

Gyrase is a unique type IIA topoisomerase that uses ATP hydrolysis to maintain the negatively supercoiled state of bacterial DNA. In order to perform its function, gyrase undergoes a sequence of conformational changes that consist of concerted gate openings, DNA cleavage, and DNA strand passage events. Structures where the transported DNA molecule (T-segment) is trapped by the A subunit have not been observed. Here we present the cryoEM structures of two oligomeric complexes of open gyrase A dimers and DNA. The protein subunits in these complexes were solved to 4 Å and 5.2 Å resolution. One of the complexes traps a linear DNA molecule, a putative T-segment, which interacts with the open gyrase A dimers in two states, representing steps either prior to or after passage through the DNA-gate. The structures locate the T-segment in important intermediate conformations of the catalytic cycle and provide insights into gyrase-DNA interactions and mechanism.

Benzene metabolites antagonize etoposide-stabilized cleavable complexes of DNA topoisomerase IIα

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 830-833 ◽  
Author(s):  
Ronda K. Baker ◽  
Ebba U. Kurz ◽  
David W. Pyatt ◽  
Richard D. Irons ◽  
David J. Kroll
Keyword(s):  
Dna Cleavage ◽  
Acute Myelogenous Leukemia ◽  
Antitumor Agents ◽  
Myelogenous Leukemia ◽  
Topoisomerase Iiα ◽  
Dna Topoisomerase ◽  
Cytogenetic Aberrations ◽  
Acute Myelogenous ◽  
Topo Ii ◽  
Cleavable Complex

Abstract Chronic exposure to benzene is associated with hematotoxicity and acute myelogenous leukemia. Inhibition of topoisomerase IIα (topo II) has been implicated in the development of benzene-induced cytogenetic aberrations. The purpose of this study was to determine the mechanism of topo II inhibition by benzene metabolites. In a DNA cleavage/relaxation assay, topo II was inhibited byp-benzoquinone and hydroquinone at 10 μM and 10 mM, respectively. On peroxidase activation, inhibition was seen with 4,4′-biphenol, hydroquinone, and catechol at 10 μM, 10 μM, and 30 μM, respectively. But, in no case was cleavable complex stabilization observed and the metabolites appeared to act at an earlier step of the enzyme cycle. In support of this conclusion, several metabolites antagonized etoposide-stabilized cleavable complex formation and inhibited topo II–DNA binding. It is therefore unlikely that benzene-induced acute myelogenous leukemia stems from events invoked for leukemogenic topo II cleavable complex-stabilizing antitumor agents.

Quinolone Action against Human Topoisomerase IIα:  Stimulation of Enzyme-Mediated Double-Stranded DNA Cleavage†

Biochemistry ◽  
2003 ◽  
Vol 42 (12) ◽  
pp. 3393-3398 ◽  
Author(s):  
Kenneth D. Bromberg ◽  
Alex B. Burgin ◽  
Neil Osheroff
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase Iiα ◽  
Double Stranded Dna ◽  
Stimulation Of

Coupling ATP hydrolysis to DNA strand passage in type IIA DNA topoisomerases

2005 ◽  
Vol 33 (6) ◽  
pp. 1460 ◽  
Author(s):  
L. Costenaro ◽  
A. Maxwell ◽  
S. Mitelheiser ◽  
A.D. Bates
Keyword(s):  
Atp Hydrolysis ◽  
Dna Topoisomerases ◽  
Dna Strand ◽  
Strand Passage

scholarly journals TOP2B: The First Thirty Years

2018 ◽  
Vol 19 (9) ◽  
pp. 2765 ◽  
Author(s):  
Caroline Austin ◽  
Ka Lee ◽  
Rebecca Swan ◽  
Mushtaq Khazeem ◽  
Catriona Manville ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Type Ii ◽  
Dna Duplex ◽  
Topoisomerase Iiα ◽  
Dna Topoisomerase ◽  
Dna Topoisomerases ◽  
Cellular Processes ◽  
Double Stranded Dna ◽  
Type Ii Dna Topoisomerases ◽  
Strand Passage

Type II DNA topoisomerases (EC 5.99.1.3) are enzymes that catalyse topological changes in DNA in an ATP dependent manner. Strand passage reactions involve passing one double stranded DNA duplex (transported helix) through a transient enzyme-bridged break in another (gated helix). This activity is required for a range of cellular processes including transcription. Vertebrates have two isoforms: topoisomerase IIα and β. Topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the 30 years since its discovery.

scholarly journals The full-length structure of Thermus scotoductus OLD defines the ATP hydrolysis properties and catalytic mechanism of Class 1 OLD family nucleases

2020 ◽  
Vol 48 (5) ◽  
pp. 2762-2776 ◽  
Author(s):  
Carl J Schiltz ◽  
Myfanwy C Adams ◽  
Joshua S Chappie
Keyword(s):  
Dna Cleavage ◽  
Spatial Organization ◽  
Catalytic Mechanism ◽  
Atp Hydrolysis ◽  
Domain Architecture ◽  
Full Length ◽  
Sequence Length ◽  
Atpase Domain ◽  
Dimerization Domain ◽  
Class 1

Abstract OLD family nucleases contain an N-terminal ATPase domain and a C-terminal Toprim domain. Homologs segregate into two classes based on primary sequence length and the presence/absence of a unique UvrD/PcrA/Rep-like helicase gene immediately downstream in the genome. Although we previously defined the catalytic machinery controlling Class 2 nuclease cleavage, degenerate conservation of the C-termini between classes precludes pinpointing the analogous residues in Class 1 enzymes by sequence alignment alone. Our Class 2 structures also provide no information on ATPase domain architecture and ATP hydrolysis. Here we present the full-length structure of the Class 1 OLD nuclease from Thermus scotoductus (Ts) at 2.20 Å resolution, which reveals a dimerization domain inserted into an N-terminal ABC ATPase fold and a C-terminal Toprim domain. Structural homology with genome maintenance proteins identifies conserved residues responsible for Ts OLD ATPase activity. Ts OLD lacks the C-terminal helical domain present in Class 2 OLD homologs yet preserves the spatial organization of the nuclease active site, arguing that OLD proteins use a conserved catalytic mechanism for DNA cleavage. We also demonstrate that mutants perturbing ATP hydrolysis or DNA cleavage in vitro impair P2 OLD-mediated killing of recBC−Escherichia coli hosts, indicating that both the ATPase and nuclease activities are required for OLD function in vivo.

Sign in / Sign up

Export Citation Format

Share Document