Single C8-Arylguanine Modifications Render Oligonucleotides in the Z-DNA Conformation under Physiological Conditions

2014 ◽  
Vol 27 (7) ◽  
pp. 1176-1186 ◽  
Author(s):  
Brian C. Train ◽  
Suzan A. Bilgesü ◽  
Emily C. Despeaux ◽  
Vorasit Vongsutilers ◽  
Peter M. Gannett
2019 ◽  
Vol 141 (19) ◽  
pp. 7758-7764 ◽  
Author(s):  
Yaping Zhang ◽  
Yixiao Cui ◽  
Ran An ◽  
Xingguo Liang ◽  
Qi Li ◽  
...  

2019 ◽  
Vol 47 (21) ◽  
pp. 11090-11102 ◽  
Author(s):  
Pablo D Dans ◽  
Alexandra Balaceanu ◽  
Marco Pasi ◽  
Alessandro S Patelli ◽  
Daiva Petkevičiūtė ◽  
...  

Abstract We present a multi-laboratory effort to describe the structural and dynamical properties of duplex B-DNA under physiological conditions. By processing a large amount of atomistic molecular dynamics simulations, we determine the sequence-dependent structural properties of DNA as expressed in the equilibrium distribution of its stochastic dynamics. Our analysis includes a study of first and second moments of the equilibrium distribution, which can be accurately captured by a harmonic model, but with nonlocal sequence-dependence. We characterize the sequence-dependent choreography of backbone and base movements modulating the non-Gaussian or anharmonic effects manifested in the higher moments of the dynamics of the duplex when sampling the equilibrium distribution. Contrary to prior assumptions, such anharmonic deformations are not rare in DNA and can play a significant role in determining DNA conformation within complexes. Polymorphisms in helical geometries are particularly prevalent for certain tetranucleotide sequence contexts and are always coupled to a complex network of coordinated changes in the backbone. The analysis of our simulations, which contain instances of all tetranucleotide sequences, allow us to extend Calladine–Dickerson rules used for decades to interpret the average geometry of DNA, leading to a set of rules with quantitative predictive power that encompass nonlocal sequence-dependence and anharmonic fluctuations.


Biochemistry ◽  
1989 ◽  
Vol 28 (12) ◽  
pp. 4923-4928 ◽  
Author(s):  
Mai Kun Teng ◽  
Yen Chywan Liaw ◽  
Gijs A. Van der Marel ◽  
Jacques H. Van Boom ◽  
Andrew H. J. Wang

2020 ◽  
Vol 92 (21) ◽  
pp. 14452-14458
Author(s):  
Yalin Li ◽  
Qing Huang ◽  
Guohua Yao ◽  
Xiaoyi Wang ◽  
Fengqiu Zhang ◽  
...  

1993 ◽  
Vol 294 (2) ◽  
pp. 419-425 ◽  
Author(s):  
T J Thomas ◽  
J R Seibold ◽  
L E Adams ◽  
E V Hess

We studied the effect of hydralazine, an antihypertensive drug with lupus-inducing side effects, on the conformation of poly(dG-m5dC).poly(dG-m5dC) and a plasmid with a 23 bp insert of (dG-dC)n.(dG-dC)n sequences. Using an e.l.i.s.a. with a monoclonal anti-(Z-DNA) antibody Z22, we found that hydralazine provoked the Z-DNA conformation in poly(dG-m5dC).poly(dG-m5dC) at 250-500 microM concentration. The supercoiled form of hydralazine-treated plasmid bound to Z22 in a gel-retardation assay. To examine further whether Z-DNA could act as an inciting agent in anti-nuclear antibody production in patients, we analysed 65 sera from 25 hypertensive patients taking hydralazine and found anti-(Z-DNA) antibodies in 82% of these sera. Sera from age-matched normal controls showed no binding to Z-DNA. Data on sera drawn sequentially from four hypertensive patients showed that antibodies were present after the drug treatment. These data demonstrate the presence of a high incidence of anti-(Z-DNA) antibodies in patients treated with hydralazine and suggest that a possible mechanism for the production of autoantibodies in drug-related lupus might involve the induction and stabilization of Z-DNA by drugs.


2015 ◽  
Vol 11 (4) ◽  
pp. e1004162 ◽  
Author(s):  
Noorain Khan ◽  
Narendar Kolimi ◽  
Thenmalarchelvi Rathinavelan

1994 ◽  
Vol 298 (2) ◽  
pp. 485-491 ◽  
Author(s):  
T J Thomas ◽  
T Thomas

Blocks of potential Z-DNA-forming (dA-dC)n.(dG-dT)n sequences are ubiquitous in eukaryotic genomes. We examined whether naturally occurring polyamines, putrescine, spermidine and spermine, could provoke the Z-DNA conformation in plasmids pDHf2 and pDHf14 with 23 and 60 bp inserts respectively of (dA-dC)n.(dG-dT)n sequences using an e.l.i.s.a. Spermidine and spermine could provoke Z-DNA conformation in these plasmids, but putrescine was ineffective. For pDHf2 and pDHf14, the concentration of spermidine at the midpoint of B-DNA to Z-DNA transition was 25 microM, whereas that of spermine was 16 microM. Polyamine structural specificity was evident in the ability of spermidine homologues to induce Z-DNA. Inorganic cations, Co(NH3)6(3+) and Ru(NH3)6(3+), were ineffective. Our experiments also showed increased binding of anti-DNA autoantibodies from lupus patients as well as autoimmune MRL-lpr/lpr mice to pDHf2 and pDHf14 in the presence of polyamines. These data demonstrate that small blocks of (dA-dC)n.(dG-dT)n sequences could assume the Z-DNA conformation in the presence of natural polyamines. Increased concentrations of polyamines in the sera of lupus patients might facilitate immune complex-formation involving circulating DNA and anti-Z-DNA antibodies.


Cell ◽  
1985 ◽  
Vol 42 (3) ◽  
pp. 713-724 ◽  
Author(s):  
Brian H. Johnston ◽  
Alexander Rich

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