scholarly journals DNA Functionality with Photoswitchable Hydrazone Cytidine

Author(s):  
Song Mao ◽  
Zhihua Chang ◽  
Ya Ying Zheng ◽  
Alexander Shekhtman ◽  
Jia Sheng

A new family of hydrazone modified cytidine phosphoramidite building block was synthesized and incorporated into DNA oligonucleotides to construct photoswitchable DNA strands. The <i>E-Z</i> isomerization triggered by the irradiation of blue light with a wavelength of 450 nm was investigated and confirmed by <sup>1</sup>H NMR and HPLC in the contexts of both nucleoside and DNA oligonucleotide. The light activated <i>Z</i> form isomer of this hydrazone-cytidine with a six-member intramolecular hydrogen bond was found to inhibit DNA synthesis in the primer extension model by using <i>Bst</i> DNA polymerase. In addition, the hydrazone modification caused the misincorporation of dATP together with dGTP into the growing DNA strand with similar selectivity, highlighting the potential G to A mutation. This work provides a novel functional DNA building block and an additional molecular tool that have potential chemical biology and bio-medicinal applications to control DNA synthesis and DNA-enzyme interactions using cell friendly blue light irradiation.

2020 ◽  
Author(s):  
Song Mao ◽  
Zhihua Chang ◽  
Ya Ying Zheng ◽  
Alexander Shekhtman ◽  
Jia Sheng

A new family of hydrazone modified cytidine phosphoramidite building block was synthesized and incorporated into DNA oligonucleotides to construct photoswitchable DNA strands. The <i>E-Z</i> isomerization triggered by the irradiation of blue light with a wavelength of 450 nm was investigated and confirmed by <sup>1</sup>H NMR and HPLC in the contexts of both nucleoside and DNA oligonucleotide. The light activated <i>Z</i> form isomer of this hydrazone-cytidine with a six-member intramolecular hydrogen bond was found to inhibit DNA synthesis in the primer extension model by using <i>Bst</i> DNA polymerase. In addition, the hydrazone modification caused the misincorporation of dATP together with dGTP into the growing DNA strand with similar selectivity, highlighting the potential G to A mutation. This work provides a novel functional DNA building block and an additional molecular tool that have potential chemical biology and bio-medicinal applications to control DNA synthesis and DNA-enzyme interactions using cell friendly blue light irradiation.


2021 ◽  
Author(s):  
Yan Zihui ◽  
Cong Liang

With the development of DNA synthesis and sequencing technologies, DNA becomes a promising medium forlong-term data storage. Three types of errors may occur in the DNA strand, insertions, deletions and substitutions,which we collectively call edit errors. It is still challenging to design a code that can correct multiple edit errors onnon-binary alphabets. In this paper, we propose a new coding schema for correcting multiple edit errors on DNAstrands by splitting the whole strand into consecutive blocks with appropriate length and correcting a single editerror in each block. Our method, called theDNA-LMcode, could be considered a generalization of the Levenshteincode combined with the marker code. We provide a linear encoding and decoding algorithm for ourDNA-LMcode.Compared to other encoding methods for DNA strands of several hundred base-pairs, ourDNA-LMcode achievedsimilar code rates and a much lower average nucleotide error rate in decoding.


2021 ◽  
Author(s):  
Yan Zihui ◽  
Cong Liang

With the development of DNA synthesis and sequencing technologies, DNA becomes a promising medium forlong-term data storage. Three types of errors may occur in the DNA strand, insertions, deletions and substitutions,which we collectively call edit errors. It is still challenging to design a code that can correct multiple edit errors onnon-binary alphabets. In this paper, we propose a new coding schema for correcting multiple edit errors on DNAstrands by splitting the whole strand into consecutive blocks with appropriate length and correcting a single editerror in each block. Our method, called theDNA-LMcode, could be considered a generalization of the Levenshteincode combined with the marker code. We provide a linear encoding and decoding algorithm for ourDNA-LMcode.Compared to other encoding methods for DNA strands of several hundred base-pairs, ourDNA-LMcode achievedsimilar code rates and a much lower average nucleotide error rate in decoding.


Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 717-726 ◽  
Author(s):  
Polina V Shcherbakova ◽  
Youri I Pavlov

Abstract The base analog 6-N-hydroxylaminopurine (HAP) induces bidirectional GC → AT and AT → GC transitions that are enhanced in DNA polymerase ϵ and δ 3′ → 5′ exonuclease-deficient yeast mutants, pol2-4 and pol3-01, respectively. We have constructed a set of isogenic strains to determine whether the DNA polymerases δ and ϵ contribute equally to proofreading of replication errors provoked by HAP during leading and lagging strand DNA synthesis. Site-specific GC → AT and AT → GC transitions in a Pol→, pol2-4 or pol3-01 genetic background were scored as reversions of ura3 missense alleles. At each site, reversion was increased in only one proofreading-deficient mutant, either pol2-4 or pol3-01, depending on the DNA strand in which HAP incorporation presumably occurred. Measurement of the HAP-induced reversion frequency of the ura3 alleles placed into chromosome III near to the defined active replication origin ARS306 in two orientations indicated that DNA polymerases ϵ and δ correct HAP-induced DNA replication errors on opposite DNA strands.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3986
Author(s):  
Cécilia Hognon ◽  
Antonio Monari

Artemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer therapy, both for the sensitization of radiotherapy and for immunotherapy. Despite its importance, its structure has been resolved only recently, and important questions concerning the arrangement of its active center, the interaction with the DNA substrate, and the catalytic mechanism remain unanswered. In this contribution, by performing extensive molecular dynamic simulations, both classically and at the hybrid quantum mechanics/molecular mechanics level, we evidenced the stable interaction modes of Artemis with a model DNA strand. We also analyzed the catalytic cycle providing the free energy profile and key transition states for the DNA cleavage reaction.


2012 ◽  
Vol 124 (45) ◽  
pp. 11429-11432 ◽  
Author(s):  
Baptiste Legrand ◽  
Christophe André ◽  
Emmanuel Wenger ◽  
Claude Didierjean ◽  
Marie Christine Averlant-Petit ◽  
...  

2006 ◽  
Vol 47 (36) ◽  
pp. 6421-6424 ◽  
Author(s):  
Ling-Hai Xie ◽  
Ting Fu ◽  
Xiao-Ya Hou ◽  
Chao Tang ◽  
Yu-Ran Hua ◽  
...  

2011 ◽  
Vol 21 (14) ◽  
pp. 5451 ◽  
Author(s):  
Zhiming Wang ◽  
Ping Lu ◽  
Shuming Chen ◽  
Zhao Gao ◽  
Fangzhong Shen ◽  
...  

2021 ◽  
Author(s):  
Denise Liano ◽  
Marco Di Antonio

AbstractGuanine-rich DNA can fold into secondary structures known as G-quadruplexes (G4s). G4s can form from a single DNA-strand (intramolecular) or from multiple DNA-strands (intermolecular), but studies on their biological functions have been often limited to intramolecular G4s, owing to the low probability of intermolecular G4s to form within genomic DNA. Herein, we report that the endogenous protein Cockayne Syndrome B (CSB) binds with picomolar affinity to intermolecular G4s, whilst displaying negligible binding towards intramolecular structures. We also observed that CSB can selectively resolve intermolecular G4s in an ATP independent fashion. Our study demonstrates that intermolecular G4s formed within ribosomal DNA are natural substrates for CSB, strongly suggesting that these structures might be formed in the nucleolus of living cells. Given that CSB loss of function elicits premature ageing phenotypes, our findings indicate that the interaction between CSB and ribosomal DNA intermolecular G4s is essential to maintain cellular homeostasis.


2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
R. A. S. Silva ◽  
J. D. T. Arruda-Neto ◽  
L. Nieto

Breaks in DNA, resulting in fragmented parts, can be produced by ionizing radiation which, in turn, is the starting point in the search for novel physical aspects of DNA strands. Double-strand breaks in particular cause disruption of the DNA strand, splitting it into several fragments. In order to study effects produced by radiation in plasmid DNA, a new simple mechanical model for this molecule is proposed. In this model, a Morse-like potential and a high-LET component are used to describe the DNA-radiation interaction. Two power laws, used to fit results of the model, suggest that, firstly, distribution of fragment size is nonextensive and, secondly, that a transition phase is present in the DNA fragment distribution pattern.


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