scholarly journals Molecular Dynamic and Docking Simulation to Prevent Thymine Dimer as the Main Reason for Skin Cancer

2021 ◽  
Vol 12 (3) ◽  
pp. 3780-3789
Keyword(s):  
Lone Pair ◽  
Docking Simulation ◽  
Dna Lesions ◽  
Model Systems ◽  
Hydrogen Binding ◽  
Ring Fusion ◽  
Thymine Dimer ◽  
Thymine Dimers ◽  
Independent Process ◽  
Total Energies

Two major types can be repaired UV-induced DNA lesions. The first one is a light-dependent process that reverts UV damage applying particular wavelengths. The second is a light-independent process that excises the light-damaged region under novo synthesis of an intact DNA. The iGEMDOCK has been used for this study, and the acceptable thymine dimer can be defined for the binding site in whole DNA structures. The DNA is worked with two thymine in a segment of nucleic acids, and iGEMDOCK can help to prepare a suitable binding between them. The total energies of the model systems are a total of several partial energies as follows: E(system) = E(bond) + E(angle) + E(torsion) +E(over) +E(vdW) + E(Coulomb) + E(Specific). EvdW +E(Coulomb) represents the dispersive and electrostatic energies contribution between all atoms, respectively. Finally, E(Specific) is system-specific energy such as lone-pair, conjugation, and hydrogen binding. The DFT and HF calculations of the thymine dimer exhibited that the ring fusion at the C5 and C6 atoms of two thymine bases produced a four-member cyclo-butane puckered ring, as well as the feature, is seen with the MPn or Moller-Pleset level. In addition, the UV radiations between 360 nm to 200 nm have been investigated for the study of thymine dimers.

scholarly journals Experimental and theoretical studies on thymine photodimerization mediated by oxidatively generated DNA lesions and epigenetic intermediates

2020 ◽  
Vol 22 (44) ◽  
pp. 25661-25668
Author(s):  
Mauricio Lineros-Rosa ◽  
Antonio Francés-Monerris ◽  
Antonio Monari ◽  
Miguel Angel Miranda ◽  
Virginie Lhiaubet-Vallet
Keyword(s):  
Dna Lesions ◽  
Theoretical Studies ◽  
Computational Studies ◽  
Thymine Dimers ◽  
Different Types ◽  
Experimental And Theoretical Studies

Combined spectroscopic and computational studies reveal that, in spite of their structural similarities, 5-formyluracil and 5-formylcytosine photosensitize cyclobutane thymine dimers through two different types of mechanisms.

scholarly journals Error-prone bypass of certain DNA lesions by the human DNA polymerase κ

2000 ◽  
Vol 14 (13) ◽  
pp. 1589-1594 ◽  
Author(s):  
Eiji Ohashi ◽  
Tomoo Ogi ◽  
Rika Kusumoto ◽  
Shigenori Iwai ◽  
Chikahide Masutani ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Polymerase ◽  
High Frequency ◽  
Dna Lesions ◽  
Human Homolog ◽  
Abasic Site ◽  
Thymine Dimer ◽  
Human Dna

The Escherichia coli protein DinB is a newly identified error-prone DNA polymerase. Recently, a human homolog of DinB was identified and named DINB1. We report that the DINB1gene encodes a DNA polymerase (designated polκ), which incorporates mismatched bases on a nondamaged template with a high frequency. Moreover, polκ bypasses an abasic site andN-2–acetylaminofluorene (AAF)-adduct in an error-prone manner but does not bypass a cis–syn or (6-4) thymine–thymine dimer or a cisplatin-adduct. Therefore, our results implicate an important role for polκ in the mutagenic bypass of certain types of DNA lesions.

DETECTION OF CYCLOBUTANE THYMINE DIMERS IN DNA OF HUMAN CELLS WITH MONOCLONAL ANTIBODIES RAISED AGAINST A THYMINE DIMER- CONTAINING TETRANUCLEOTIDE

1988 ◽  
Vol 48 (5) ◽  
pp. 627-633 ◽  
Author(s):  
Len Roza ◽  
Kees J. M. Wulp ◽  
Sandra J. MacFarlane ◽  
Paul H. M.Lohman ◽  
Robert A. Baan
Keyword(s):  
Monoclonal Antibodies ◽  
Human Cells ◽  
Thymine Dimer ◽  
Thymine Dimers

scholarly journals Metabolism, Genomics, and DNA Repair in the Mouse Aging Liver

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Michel Lebel ◽  
Nadja C. de Souza-Pinto ◽  
Vilhelm A. Bohr
Keyword(s):  
Dna Repair ◽  
Point Mutations ◽  
Dna Lesions ◽  
Model Systems ◽  
Rodent Models ◽  
Waste Products ◽  
Related Disease ◽  
Age Related ◽  
Significant Impairment ◽  
And Function

The liver plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products, thereby maintaining body homeostasis. The liver undergoes substantial changes in structure and function within old age. Such changes are associated with significant impairment of many hepatic metabolic and detoxification activities, with implications for systemic aging and age-related disease. It has become clear, using rodent models as biological tools, that genetic instability in the form of gross DNA rearrangements or point mutations accumulate in the liver with age. DNA lesions, such as oxidized bases or persistent breaks, increase with age and correlate well with the presence of senescent hepatocytes. The level of DNA damage and/or mutation can be affected by changes in carcinogen activation, decreased ability to repair DNA, or a combination of these factors. This paper covers some of the DNA repair pathways affecting liver homeostasis with age using rodents as model systems.

scholarly journals The interplay of supercoiling and thymine dimers in DNA

2021 ◽  
Author(s):  
Wilber Lim ◽  
Ferdinando Randisi ◽  
Jonathan P. K. Doye ◽  
Ard A. Louis
Keyword(s):  
Dna Supercoiling ◽  
Bend Angle ◽  
Experimental Investigations ◽  
Local Defect ◽  
Thymine Dimer ◽  
Biologically Relevant ◽  
Repair Enzymes ◽  
Damage Repair ◽  
Thymine Dimers ◽  
Dynamics Simulations

AbstractThymine dimers are a major mutagenic photoproduct induced by UV radiation. While they have been the subject of extensive theoretical and experimental investigations, questions of how DNA supercoiling affects local defect properties, or, conversely, how the presence of such defects changes global supercoiled structure, are largely unexplored. Here we introduce a model of thymine dimers in the oxDNA forcefield, and validate it by comparison to melting experiments and structural measurements of the thymine dimer induced bend angle. We performed extensive molecular dynamics simulations of double-stranded DNA as a function of external twist and force. Compared to undamaged DNA, the presence of a thymine dimer lowers the supercoiling densities at which plectonemes and bubbles occur. For biologically relevant supercoiling densities and forces, thymine dimers can preferentially segregate to the tips of the plectonemes, where they enhance the probability of a localized tip-bubble. This mechanism increases the probability of highly bent and denatured states at the thymine dimer site, which may facilitate repair enzyme binding. Thymine dimer-induced tip-bubbles also pin plectonemes, which may help repair enzymes to locate damage. We hypothesize that the interplay of supercoiling and local defects plays an important role for a wider set of DNA damage repair systems.

Ultraviolet light induced thymine dimers and repair processes in the alga Eudorina elegans

1972 ◽  
Vol 18 (12) ◽  
pp. 1809-1815 ◽  
Author(s):  
C. L. Kemp ◽  
M. S. Tsao ◽  
G. Thorson
Keyword(s):  
Visible Light ◽  
Ultraviolet Light ◽  
Green Alga ◽  
Uv Irradiation ◽  
Excision Repair ◽  
Uv Exposure ◽  
Dark Repair ◽  
Thymine Dimer ◽  
Thymine Dimers ◽  
Cellular Dna

A fraction of the cellular DNA of the colonial green alga Eudorina elegans strain 1193 can be specifically labeled with 3H-thymidine but not by 3H-thymine. Ultraviolet (UV) irradiation of E. elegans leads to the production of thymine dimers as determined by extraction, hydrolysis, and chromatography of 3H-thymidine-labeled cells. Removal of dimers occurs by processes involving visible light (photoreactivation), but dark repair (excision repair) has not been detected in the labeled fraction. A relationship between UV exposure and thymine dimer production has been determined.

scholarly journals Variable inhibition of unwinding rates of DNA catalyzed by the SARS-Cov-2 (COV19) helicase nsp13 by structurally distinct single DNA lesions.

2021 ◽  
Author(s):  
Ana H. Sales ◽  
Sam Ciervo ◽  
Tania Lupoli ◽  
Vladimir Shafirovich ◽  
Nicholas E Geacintov
Keyword(s):  
Structural Features ◽  
Dna Lesions ◽  
Pyrimidine Dimer ◽  
Helicase Activity ◽  
Thymine Dimers ◽  
Guanine Adducts ◽  
Bulky Dna Adducts ◽  
A Minor ◽  
The Impact ◽  
Kinetics Of

The SARS 2 (Covid 19) helicase nsp13 plays a critically important role in the replication of the Corona virus by unwinding double-stranded RNA (and DNA) with a 5 prime to 3 prime strand polarity. Here we explored the impact of single, structurally defined covalent DNA lesions on the helicase activity of nsp13 in aqueous solutions, The objectives were to derive mechanistic insights into the relationships between the structures of DNA lesions, the DNA distortions that they engender, and the inhibition of helicase activity. The lesions included two bulky stereoisomeric N2-guanine adducts derived from the reactions of benzo[a]pyrene diol epoxide with DNA. The trans-adduct assumes a minor groove conformation, while the cis-product adopts a base-displaced intercalated conformation. The non-bulky DNA lesions included the intra-strand cross-linked thymine dimers, the cis-syn-cyclobutane pyrimidine dimer, and the pyrimidine (6–4) pyrimidone photoproduct. All four lesions strongly inhibit the helicase activity of nsp13, The UV photolesions feature a 2 - 5-fold smaller inhibition of the nsp13 unwinding activity than the bulky DNA adducts, and the kinetics of these two pairs of DNA lesions are also different. The connections between the structural features of these four DNA lesions and their impact on nsp13 unwinding efficiencies are discussed.

Electronic Nature of α-Methoxy, Amino, Cyano, and Mercapto Nitrones

1993 ◽  
Vol 58 (1) ◽  
pp. 125-141 ◽  
Author(s):  
David E. Gallis ◽  
James A. Warshaw ◽  
Bruce J. Acken ◽  
DeLanson R. Crist
Keyword(s):  
Bond Order ◽  
Cyano Group ◽  
Energy Levels ◽  
Lone Pair ◽  
Model Systems ◽  
Electronic Nature ◽  
Versus Model ◽  
Mndo Calculations ◽  
Reverse Substituent Effect ◽  
C Nmr

The electronic nature of various C-substituted nitrones was investigated by IR spectroscopy and 13C NMR as well as MNDO calculations. These include α-methoxy nitrones (imidate N-oxides) RC(OMe)=N(O)t-Bu with R = p-MeOC6H4 (Ia), C6H5 (Ib), p-NO2C6H4 (Ic), and H (Id) and nitrones YCH=N(O)t-Bu with Y = CN (IIIa), n-BuS (IIIb), C6H5CH2NH (IIIc). Upfield 13C shifts of C(α), the iminyl (C=N) carbon, of imidate N-oxides I versus the corresponding imidates are less than the usual upfield shifts of imine N-oxides versus imines, suggesting less buildup of electron density on C(α) in the case of alcoxy nitrones. Charge density and π bond order values from MNDO calculations for C-methoxy-C-phenyl nitrones versus model systems confirm this result and indicate a more localized C=N π bond in nitrones bearing an α-methoxy group. For N-tert-butyl nitrones with an α heteroatom (nitrogen or sulfur), phenyl, or cyano group, C(α) shifts move downfield for π-donating groups and upfield for π-accepting groups. This "reverse substituent effect" as well as C=N stretching frequencies can also be readily explained by C=N π bond containment by lone pair groups. The reported enhanced cycloaddition reactivity of α-alkoxy nitrones and their electrochemical behavior are discussed in terms of HOMO energy levels.

σ-Hole interactions in small-molecule compounds containing divalent sulfur groups R 1—S—R 2

2020 ◽  
Vol 76 (4) ◽  
pp. 707-718
Author(s):  
Albert S. Lundemba ◽  
Dikima D. Bibelayi ◽  
Peter A. Wood ◽  
Juliette Pradon ◽  
Zéphyrin G. Yav
Keyword(s):  
Small Molecule ◽  
Crystal Engineering ◽  
Noncovalent Interactions ◽  
Interaction Strength ◽  
Lone Pair ◽  
Structural Data ◽  
Data Bank ◽  
Nbo Analysis ◽  
Model Systems ◽  
Divalent Sulfur

Hydrogen bonds, aromatic stacking contacts and σ-hole interactions are all noncovalent interactions commonly observed in biological systems. Structural data derived from the Protein Data Bank showed that methionine residues can interact with oxygen atoms through directional S...O contacts in the protein core. In the present work, the Cambridge Structural Database (CSD) was used in conjunction with ab initio calculations to explore the σ-hole interaction properties of small-molecule compounds containing divalent sulfur. CSD surveys showed that 7095 structures contained R 1—S—R 2 groups that interact with electronegative atoms like N, O, S and Cl. Frequencies of occurrence and geometries of the interaction were dependent on the nature of R 1 and R 2, and the hybridization of carbon atoms in C,C—S, and C,S—S fragments. The most common interactions in terms of frequency of occurrence were C,C—S...O, C,C—S...N and C,C—S...S with predominance of Csp 2. The strength of the chalcogen interaction increased when enhancing the electron-withdrawing character of the substituents. The most positive electrostatic potentials (V S,max; illustrating positive σ-holes) calculated on R 1—S—R 2 groups were located on the S atom, in the S—R 1 and S—R 2 extensions, and increased with electron-withdrawing R 1 and R 2 substituents like the interaction strength did. As with geometric data derived from the CSD, interaction geometries calculated for some model systems and representative CSD compounds suggested that the interactions were directed in the extensions of S—R 1 and S—R 2 bonds. The values of complexation energies supported attractive interactions between σ-hole bond donors and acceptors, enhanced by dispersion. The interactions of R 1—S—R 2 with large V S,max and nucleophiles with large negative V S,min coherently provided more negative energies. According to NBO analysis, chalcogen interactions consisted of charge transfer from a nucleophile lone pair to an S—R 1 or S—R 2 antibonding orbital. The directional σ-hole interactions at R 1—S—R 2 can be useful in crystal engineering and the area of supramolecular biochemistry.

scholarly journals On the Importance of σ–Hole Interactions in Crystal Structures

Crystals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1205
Author(s):  
Antonio Frontera ◽  
Antonio Bauzá
Keyword(s):  
Lewis Acids ◽  
Noncovalent Interactions ◽  
Noble Gas ◽  
Lone Pair ◽  
Halogen Bonding ◽  
Lewis Base ◽  
Model Systems ◽  
Aromatic Rings ◽  
Potential Surfaces ◽  
Dual Character

Elements from groups 14–18 and periods 3–6 commonly behave as Lewis acids, which are involved in directional noncovalent interactions (NCI) with electron-rich species (lone pair donors), π systems (aromatic rings, triple and double bonds) as well as nonnucleophilic anions (BF4−, PF6−, ClO4−, etc.). Moreover, elements of groups 15 to 17 are also able to act as Lewis bases (from one to three available lone pairs, respectively), thus presenting a dual character. These emerging NCIs where the main group element behaves as Lewis base, belong to the σ–hole family of interactions. Particularly (i) tetrel bonding for elements belonging to group 14, (ii) pnictogen bonding for group 15, (iii) chalcogen bonding for group 16, (iv) halogen bonding for group 17, and (v) noble gas bondings for group 18. In general, σ–hole interactions exhibit different features when moving along the same group (offering larger and more positive σ–holes) or the same row (presenting a different number of available σ–holes and directionality) of the periodic table. This is illustrated in this review by using several examples retrieved from the Cambridge Structural Database (CSD), especially focused on σ–hole interactions, complemented with molecular electrostatic potential surfaces of model systems.

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