scholarly journals Bimodal Recognition of DNA Geometry by Human Topoisomerase IIα: Preferential Relaxation of Positively Supercoiled DNA Requires Elements in the C-Terminal Domain†

Biochemistry ◽  
2008 ◽  
Vol 47 (50) ◽  
pp. 13169-13178 ◽  
Author(s):  
A. Kathleen McClendon ◽  
Amanda C. Gentry ◽  
Jennifer S. Dickey ◽  
Marie Brinch ◽  
Simon Bendsen ◽  
...  
Keyword(s):  
Topoisomerase Iiα ◽  
Supercoiled Dna ◽  
Terminal Domain ◽  
Dna Geometry

scholarly journals Role of a tryptophan anchor in human topoisomerase I structure, function and inhibition

2008 ◽  
Vol 411 (3) ◽  
pp. 523-530 ◽  
Author(s):  
Gary S. Laco ◽  
Yves Pommier
Keyword(s):  
Amino Acids ◽  
Topoisomerase I ◽  
Electrostatic Interactions ◽  
Functional Domain ◽  
Site Mutation ◽  
Supercoiled Dna ◽  
Terminal Domain ◽  
Tryptophan Residues ◽  
N Terminus

Human Top1 (topoisomerase I) relaxes supercoiled DNA during cell division and transcription. Top1 is composed of 765 amino acids and contains an unstructured N-terminal domain of 200 amino acids, and a structured functional domain of 565 amino acids that binds and relaxes supercoiled DNA. In the present study we examined the region spanning the junction of the N-terminal domain and functional domain (junction region). Analysis of several published Top1 structures revealed that three tryptophan residues formed a network of aromatic stacking interactions and electrostatic interactions that anchored the N-terminus of the functional domain to sub-domains containing the nose cone and active site. Mutation of the three tryptophan residues (Trp203/Trp205/Trp206) to an alanine residue, either individually or together, in silico revealed that the individual tryptophan residue's contribution to the tryptophan ‘anchor’ was additive. When the three tryptophan residues were mutated to alanine in vitro, the resulting mutant Top1 differed from wild-type Top1 in that it lacked processivity, exhibited resistance to camptothecin and was inactivated by urea. The results indicated that the tryptophan anchor stabilized the N-terminus of the functional domain and prevented the loss of Top1 structure and function.

scholarly journals The Bacillus subtilis Primosomal Protein DnaD Untwists Supercoiled DNA

2006 ◽  
Vol 188 (15) ◽  
pp. 5487-5493 ◽  
Author(s):  
Wenke Zhang ◽  
Stephanie Allen ◽  
Clive J. Roberts ◽  
Panos Soultanas
Keyword(s):  
Bacillus Subtilis ◽  
Dna Replication ◽  
Supercoiled Dna ◽  
Linking Number ◽  
Terminal Domain ◽  
Initiation Of Replication ◽  
Open Circular ◽  
Initiation Of Dna Replication ◽  
Dna Remodeling

ABSTRACT The essential Bacillus subtilis DnaD and DnaB proteins have been implicated in the initiation of DNA replication. Recently, DNA remodeling activities associated with both proteins were discovered that could provide a link between global or local nucleoid remodeling and initiation of replication. DnaD forms scaffolds and opens up supercoiled plasmids without nicking to form open circular complexes, while DnaB acts as a lateral compaction protein. Here we show that DnaD-mediated opening of supercoiled plasmids is accompanied by significant untwisting of DNA. The net result is the conversion of writhe (Wr) into negative twist (Tw), thus maintaining the linking number (Lk) constant. These changes in supercoiling will reduce the considerable energy required to open up closed circular plectonemic DNA and may be significant in the priming of DNA replication. By comparison, DnaB does not affect significantly the supercoiling of plasmids. Binding of the DnaD C-terminal domain (Cd) to DNA is not sufficient to convert Wr into negative Tw, implying that the formation of scaffolds is essential for duplex untwisting. Overall, our data suggest that the topological effects of the two proteins on supercoiled DNA are different; DnaD opens up, untwists and converts plectonemic DNA to a more paranemic form, whereas DnaB does not affect supercoiling significantly and condenses DNA only via its lateral compaction activity. The significance of these findings in the initiation of DNA replication is discussed.

scholarly journals Exploration of the Role of the C-Terminal Domain of Human DNA Topoisomerase IIα in Catalytic Activity

ACS Omega ◽  
2021 ◽  
Vol 6 (40) ◽  
pp. 25892-25903
Author(s):  
Ashley C. Dougherty ◽  
Mariam G. Hawaz ◽  
Kristine G. Hoang ◽  
Judy Trac ◽  
Jacob M. Keck ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Topoisomerase Iiα ◽  
Dna Topoisomerase ◽  
Terminal Domain ◽  
Human Dna ◽  
Dna Topoisomerase Iiα

The N-Terminal Domain of Human Topoisomerase IIα Is a DNA-Dependent ATPase†

Biochemistry ◽  
1998 ◽  
Vol 37 (48) ◽  
pp. 16997-17004 ◽  
Author(s):  
Laurence P. Gardiner ◽  
David I. Roper ◽  
Timothy R. Hammonds ◽  
Anthony Maxwell
Keyword(s):  
Topoisomerase Iiα ◽  
Terminal Domain ◽  
Dependent Atpase

scholarly journals Human Topoisomerase IIα Rapidly Relaxes Positively Supercoiled DNA

2005 ◽  
Vol 280 (47) ◽  
pp. 39337-39345 ◽  
Author(s):  
A. Kathleen McClendon ◽  
A. Chapin Rodriguez ◽  
Neil Osheroff
Keyword(s):  
Topoisomerase Iiα ◽  
Supercoiled Dna

scholarly journals Ability of Viral Topoisomerase II To Discern the Handedness of Supercoiled DNA:  Bimodal Recognition of DNA Geometry by Type II Enzymes†

Biochemistry ◽  
2006 ◽  
Vol 45 (38) ◽  
pp. 11674-11680 ◽  
Author(s):  
A. Kathleen McClendon ◽  
Jennifer S. Dickey ◽  
Neil Osheroff
Keyword(s):  
Topoisomerase Ii ◽  
Type Ii ◽  
Supercoiled Dna ◽  
Dna Geometry

scholarly journals SUMOylation of the C-terminal domain of DNA topoisomerase IIα regulates the centromeric localization of Claspin

Cell Cycle ◽  
2015 ◽  
Vol 14 (17) ◽  
pp. 2777-2784 ◽  
Author(s):  
Hyunju Ryu ◽  
Makoto M Yoshida ◽  
Vinidhra Sridharan ◽  
Akiko Kumagai ◽  
William G Dunphy ◽  
...  
Keyword(s):  
Topoisomerase Iiα ◽  
Dna Topoisomerase ◽  
Terminal Domain ◽  
Dna Topoisomerase Iiα

Preferential binding of tumor suppressor p53 to positively or negatively supercoiled DNA involves the C-terminal domain 1 1Edited by K. Yamamoto

1999 ◽  
Vol 292 (2) ◽  
pp. 241-249 ◽  
Author(s):  
Sharlyn J Mazur ◽  
Kazuyasu Sakaguchi ◽  
Ettore Appella ◽  
Xin Wei Wang ◽  
Curtis C Harris ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor P53 ◽  
Supercoiled Dna ◽  
Terminal Domain ◽  
Preferential Binding
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