scholarly journals Bases alternatives et organismes synthétiques

2018 ◽  
Vol 34 (2) ◽  
pp. 179-182 ◽  
Author(s):  
Bertrand Jordan

Alternative bases that can fit into the DNA double helix have now been used in vivo to direct the synthesis of proteins incorporating unnatural amino acids. This bioengineering feat is significant at both the conceptual and the practical levels

2021 ◽  
Author(s):  
Babu Sudhamalla ◽  
Anirban Roy ◽  
Soumen Barman ◽  
Jyotirmayee Padhan

The site-specific installation of light-activable crosslinker unnatural amino acids offers a powerful approach to trap transient protein-protein interactions both in vitro and in vivo. Herein, we engineer a bromodomain to...


Life ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 18 ◽  
Author(s):  
Christian J. Michel

We study the distribution of new classes of motifs in genes, a research field that has not been investigated to date. A single-frame motif SF has no trinucleotide in reading frame (frame 0) that occurs in a shifted frame (frame 1 or 2), e.g., the dicodon AAACAA is SF as the trinucleotides AAA and CAA do not occur in a shifted frame. A motif which is not single-frame SF is multiple-frame MF. Several classes of MF motifs are defined and analysed. The distributions of single-frame SF motifs (associated with an unambiguous trinucleotide decoding in the two 5'–3' and 3'–5' directions) and 5′ unambiguous motifs 5'U (associated with an unambiguous trinucleotide decoding in the 5'–3' direction only) are analysed without and with constraints. The constraints studied are: initiation and stop codons, periodic codons AAA,CCC,GGG,TTT, antiparallel complementarity and parallel complementarity. Taken together, these results suggest that the complementarity property involved in the antiparallel (DNA double helix, RNA stem) and parallel sequences could also be fundamental for coding genes with an unambiguous trinucleotide decoding in the two 5'–3' and 3'–5' directions or the 5'–3' direction only. Furthermore, the single-frame motifs SF with a property of trinucleotide decoding and the framing motifs F (also called circular code motifs; first introduced by Michel (2012)) with a property of reading frame decoding may have been involved in the early life genes to build the modern genetic code and the extant genes. They could have been involved in the stage without anticodon-amino acid interactions or in the Implicated Site Nucleotides (ISN) of RNA interacting with the amino acids. Finally, the SF and MF dipeptides associated with the SF and MF dicodons, respectively, are studied and their importance for biology and the origin of life discussed.


2016 ◽  
Vol 30 (08) ◽  
pp. 1650117 ◽  
Author(s):  
Gundolf Schenk ◽  
Brad Krajina ◽  
Andrew Spakowitz ◽  
Sebastian Doniach

In vivo chromosomal behavior is dictated by the organization of genomic DNA at length scales ranging from nanometers to microns. At these disparate scales, the DNA conformation is influenced by a range of proteins that package, twist and disentangle the DNA double helix, leading to a complex hierarchical structure that remains undetermined. Thus, there is a critical need for methods of structural characterization of DNA that can accommodate complex environmental conditions over biologically relevant length scales. Based on multiscale molecular simulations, we report on the possibility of measuring supercoiling in complex environments using angular correlations of scattered X-rays resulting from X-ray free electron laser (xFEL) experiments. We recently demonstrated the observation of structural detail for solutions of randomly oriented metallic nanoparticles [D. Mendez et al., Philos. Trans. R. Soc. B 360 (2014) 20130315]. Here, we argue, based on simulations, that correlated X-ray scattering (CXS) has the potential for measuring the distribution of DNA folds in complex environments, on the scale of a few persistence lengths.


1999 ◽  
Vol 276 (1) ◽  
pp. R128-R135 ◽  
Author(s):  
Christiaan Leeuwenburgh ◽  
Polly A. Hansen ◽  
John O. Holloszy ◽  
Jay W. Heinecke

Oxidative damage of proteins has been implicated in disease and aging. In vitro studies demonstrate that two unnatural amino acids, o,o′-dityrosine and o-tyrosine, are stable markers of protein oxidation. We have investigated the possibility that assaying these compounds in urine could provide a noninvasive way to determine levels of protein oxidation in vivo. Isotope dilution gas chromatography-mass spectrometry was used to quantify levels of o,o′-dityrosine and o-tyrosine in skeletal muscle and urine of aging rats subjected to two interventions: 1) dietary antioxidant supplementation and 2) exercise training. In both sedentary rats and exercise-trained rats, antioxidant therapy reduced levels of protein-bound o,o′-dityrosine in skeletal muscle. In contrast, antioxidant therapy or exercise training minimally affected o-tyrosine levels in this tissue. Levels of the oxidized amino acids in urine samples mirrored those of skeletal muscle proteins. Quantification of the levels of oxidized amino acids in urine may thus serve as a noninvasive measure of oxidative stress in vivo because they change in parallel with levels of protein-bound oxidized amino acids in skeletal muscle.


2021 ◽  
Author(s):  
Shaokun Chen ◽  
Weiyi Lai ◽  
Zhiyi Zhao ◽  
Ning Zhang ◽  
Yan Liu ◽  
...  

Abstract Abundant RNA N6-methyladenine (m6A) is degraded in RNA decay and potentially induces aberrant DNA N6-methyladenine (6mA) misincorporation. Biophysically, like truly methylated product DNA 6mA, misincorporated 6mA also destabilizes the DNA double helix and thus ditto affects DNA replication and transcription. By heavy stable isotope tracing, we demonstrate that intracellular degradation of RNA m6A cannot induce any misincorporated DNA 6mA, unveiling the existence of a catabolism checkpoint that blocks DNA 6mA misincorporation. We further show that the deaminase ADAL preferentially catabolizes N6-methyl-2’-deoxyadenosine monophosphate (6mdAMP) in vitro and in vivo, and adenylate kinase 1 restricts the phosphorylation rate of 6mdAMP, together contributing to the identified checkpoint. Noteworthy, low ADAL expression reduces dramatically the patient survival in four cancers. Collectively, our data strongly support a pivotal role of ADAL in the suppression of 6mA misincorporation and implicate that both ADAL and misincorporated 6mA may mark cancer abnormalities.


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