Characterization of Two CHO Variants in Respect to MNNG-Induced Cell Killing, Mutations, and Repair of Methylated DNA Bases

1986 ◽  
pp. 447-451
Author(s):  
R. Goth-Goldstein ◽  
M. Hughes
Keyword(s):  
Cell Killing ◽  
Dna Bases ◽  
Methylated Dna

Partition Coefficients of Methylated DNA Bases Obtained from Free Energy Calculations with Molecular Electron Density Derived Atomic Charges.

2018 ◽  
Author(s):  
Alejandro Lara ◽  
Maximiliano Riquelme ◽  
Esteban Vöhringer-Martinez
Keyword(s):  
Electron Density ◽  
Partition Coefficients ◽  
Dna Bases ◽  
Atomic Charges ◽  
Free Energies ◽  
Solvation Model ◽  
Minimal Basis ◽  
Methylated Dna ◽  
Implicit Solvation Model ◽  
Good Agreement

<div> <div> <div> <p>Partition coefficients serve in various areas as pharmacology and environmental sciences to predict the hydrophobicity of different substances. Recently, they have been also used to address the accuracy of force fields for various organic compounds and specifically the methylated DNA bases. In this study atomic charges were derived by different partitioning methods (Hirshfeld and Minimal Basis Iterative Stockholder) directly from the electron density obtained by electronic structure calculations in vac- uum, with an implicit solvation model or with explicit solvation taking the dynamics of the solute and the solvent into account. To test the ability of these charges to describe electrostatic interactions in force fields for condensed phases the original atomic charges of the AMBER99 force field were replaced with the new atomic charges and combined with different solvent models to obtain the hydration and chloroform solvation free energies by molecular dynamics simulations. Chloroform-water partition coefficients derived from the obtained free energies were compared to experimental and previously reported values obtained with the GAFF or the AMBER-99 force field. The results show that good agreement with experimental data is obtained when the polarization of the electron density by the solvent has been taken into account deriving the atomic charges of polar DNA bases and when the energy needed to polarize the electron den- sity of the solute has been considered in the transfer free energy. These results were further confirmed by hydration free energies of polar and aromatic amino acid side chain analogues. Comparison of the two partitioning methods Hirsheld-I and Minimal Basis Iterative Stockholder (MBIS) revealed some deficiencies in the Hirshfeld-I method related to nonexistent isolated anionic nitrogen pro-atoms used in the method. Hydration free energies and partitioning coefficients obtained with atomic charges from the MBIS partitioning method accounting for polarization by the implicit solvation model are in good agreement with the experimental values. </p> </div> </div> </div>

scholarly journals Identification and Functional Characterization of the p66/p68 Components of the MeCP1 Complex

2002 ◽  
Vol 22 (2) ◽  
pp. 536-546 ◽  
Author(s):  
Qin Feng ◽  
Ru Cao ◽  
Li Xia ◽  
Hediye Erdjument-Bromage ◽  
Paul Tempst ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Cpg Dinucleotides ◽  
Methylated Dna ◽  
Major Mechanism ◽  
Preferential Binding ◽  
Dna Silencing ◽  
The Individual ◽  
Identification And Characterization ◽  
Eukaryotic Genomes

ABSTRACT Methylation of cytosine at CpG dinucleotides is a common feature of many higher eukaryotic genomes. A major biological consequence of DNA methylation is gene silencing. Increasing evidence indicates that recruitment of histone deacetylase complexes by methyl-CpG-binding proteins is a major mechanism of methylated DNA silencing. We have previously reported that the MeCP1 protein complex represses transcription through preferential binding, remodeling, and deacetylation of methylated nucleosomes. To understand the molecular mechanism of the functioning of the MeCP1 complex, the individual components of the MeCP1 complex need to be characterized. In this paper, we report the identification and functional characterization of the p66 and p68 components of the MeCP1 complex. We provide evidence that the two components are different forms of the same zinc finger-containing protein. Analysis of the p66 homologs from different organisms revealed two highly conserved regions, CR1 and CR2. While CR1 is involved in the association of p66 with other MeCP1 components, CR2 plays an important role in targeting p66 and MBD3 to specific loci. Thus, our study not only completes the identification of the MeCP1 components but also reveals the potential function of p66 in MeCP1 complex targeting. The identification and characterization of all the MeCP1 components set the stage for reconstitution of the MeCP1 complex.

scholarly journals A novel BH3 ligand that selectively targets Mcl-1 reveals that apoptosis can proceed without Mcl-1 degradation

2008 ◽  
Vol 180 (2) ◽  
pp. 341-355 ◽  
Author(s):  
Erinna F. Lee ◽  
Peter E. Czabotar ◽  
Mark F. van Delft ◽  
Ewa M. Michalak ◽  
Michelle J. Boyle ◽  
...  
Keyword(s):  
Structural Study ◽  
Proteasomal Degradation ◽  
Cell Killing ◽  
Disease Relapse ◽  
Survival Factor ◽  
Functional Inactivation ◽  
Binding Groove

Like Bcl-2, Mcl-1 is an important survival factor for many cancers, its expression contributing to chemoresistance and disease relapse. However, unlike other prosurvival Bcl-2–like proteins, Mcl-1 stability is acutely regulated. For example, the Bcl-2 homology 3 (BH3)–only protein Noxa, which preferentially binds to Mcl-1, also targets it for proteasomal degradation. In this paper, we describe the discovery and characterization of a novel BH3-like ligand derived from Bim, BimS2A, which is highly selective for Mcl-1. Unlike Noxa, BimS2A is unable to trigger Mcl-1 degradation, yet, like Noxa, BimS2A promotes cell killing only when Bcl-xL is absent or neutralized. Furthermore, killing by endogenous Bim is not associated with Mcl-1 degradation. Thus, functional inactivation of Mcl-1 does not always require its elimination. Rather, it can be efficiently antagonized by a BH3-like ligand tightly engaging its binding groove, which is confirmed here with a structural study. Our data have important implications for the discovery of compounds that might kill cells whose survival depends on Mcl-1.

Interaction of beryllium derivatives with N-methylated DNA bases: 9-methylguanine and 1-methylcytosine

Tetrahedron ◽  
2016 ◽  
Vol 72 (16) ◽  
pp. 1978-1983 ◽  
Author(s):  
Marta Marín-Luna ◽  
Ibon Alkorta ◽  
José Elguero
Keyword(s):  
Dna Bases ◽  
Methylated Dna

Ambiguous coding is required for the lethal interaction between methylated DNA bases and DNA mismatch repair

DNA Repair ◽  
2002 ◽  
Vol 1 (4) ◽  
pp. 275-286 ◽  
Author(s):  
Andrew Massey ◽  
Yao-Zhong Xu ◽  
Peter Karran
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Dna Bases ◽  
Methylated Dna ◽  
Dna Mismatch

scholarly journals Cloning and Characterization of a New Site-Specific Methyl-Directed ElmI Endonuclease Recognizing and Cleaving C5-methylated DNA Sequence 5’-G(5mC)^NG(5mC)-3’

Acta Naturae ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 117-125 ◽  
Author(s):  
V. A. Chernukhin ◽  
D. A. Gonchar ◽  
M. A. Abdurashitov ◽  
O. A. Belichenko ◽  
V. S. Dedkov ◽  
...  
Keyword(s):  
Dna Sequence ◽  
Amino Acid Sequences ◽  
Open Reading Frames ◽  
Site Specific ◽  
Pcr Screening ◽  
Methylated Dna ◽  
Chromatographic Techniques ◽  
Dna Fragment ◽  
Reading Frames

Putative open reading frames of MD-endonucleases have been identified in Enterobacteria genomes as a result of the search for amino acid sequences homologous to MD-endonuclease BisI. A highly conserved DNA primary structure of these open reading frames in different genera of Enterobacteria (Escherichia, Klebsiella and Cronobacter) has allowed researchers to create primers for PCR screening, which was carried out on Enterobacteria DNA collected from natural sources. The DNA fragment, about 440 bp in length, was amplified by use of the genomic DNA of a wild E.coli LM N17 strain as a template and was inserted into the pMTL22 vector. Endonuclease activity was detected in an E.coli ER 2267 strain transformed with the obtained construction. A new enzyme named ElmI was purified by chromatographic techniques from the recombinant strain biomass. It was discovered that similarly to BisI this enzyme specifically cleaves the methylated DNA sequence 5-GCNGC- 3 before the central nucleotide N if this sequence contains two 5-methylcytosines. However, unlike BisI, ElmI more efficiently cleaves this sequence if more than two cytosine residues are methylated.

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