A Nuclear Spin Selective Control over the DNA Repair Key Enzyme Might Renovate the Cancer–Fight Paradigm. DNA Polymerase Beta to Engage with a Magnetic Isotope Effect
Journal Title: JOURNAL OF ADVANCES IN CHEMISTRY - Year 2013, Vol 4, Issue 3
Abstract
DNA Polymerase Beta (EC 2.7.7.7) is found to be operated by magnetic isotope effect (MIE) of Calcium once the Mg2+ ions replaced with the stable 43Ca2+ isotopes inside the enzyme catalytic sites. The isotope mentioned is the only paramagnetic species of the Calcium isotopic set with a 0.135 natural abundance value and the negative 7/2 nuclear spin providing a nuclear magnetic moment equal to 1.317 Bohr magnetons. As compared to the Mg/40Ca substitution, a 2.25-fold enzyme inhibition has been shown to provethe43Ca-MIE dependent mode of the catalysis turning down.An ion-radical mechanism based on the singlet – triplet conversion of the enzyme generated intermediates (ion-radical pairs) is found to be engaged once the paramagnetic metal isotope involved into the catalysis studied.The MIE promotes a primary reaction in DNA synthesis constituting in electron transfer between the ion – radical forming partners, [Ca(H2O)n2+] and [Ca2+(dNTP)]. Once the metal isotope substitution takes place inside just one of two DNA Polymerase Beta catalytic sites, a consequent43Ca – promoted inhibition leads to a residual synthesis of shorted DNA fragments that counts 25 – 35 nucleotides in length contrasting with the 180n – 210n DNA produced by either intact or40Ca – loaded polymerase. Being occurred simultaneously with a marked MIE – promoted enzyme inhibition, this fact itself makes possible to consider these short (“size-invalidâ€) DNA segments hardly efficient in the DNA base – excision repair. The latter is a survival factor in leukemic cells where the DNApolβ was found overexpressed. That supports a standpoint considering theDNApolβ a legitimate target for antitumor agents since its inhibition deprives the malignant cell from a DNA base – excision repair in neoplasma. A possible trend making role of these data in the current developments on a novel concept - establishing chemical background for cancer therapies is in a focus.
Authors and Affiliations
Oleg A. Shatalov, Maxim E. Grigoryev, Alexander A. Bukhvostov, Dmitry A. Kuznetsov
Keywords
Related Articles
- EP ID EP652580
- DOI 10.24297/jac.v4i3.953
- Views 192
- Downloads 0
Molecular Simulation of Hyperbranched Polyester
A new types of hyperbranched polyester was synthesized by the 2,2-bis(hydroxymethyl) propionic acid as an AB2-type monomer and glycerol as the core moiety. Molecular weights were confirmed by Gel Permeation Chromatograph...
ASSESSMENT OF SEASONAL PHYSICO-CHEMICAL PARAMETERS OF OGUTA LAKE, NIGERIA.
Seasonal variation of physico-chemical variables of Oguta Lake, Nigeria was studied. Results obtained using standard analytical methods indicated that in the rainy and dry seasons (July and August) and (October and Novem...
An Investigation of Ultra-Wideband Filters for Cognitive Radio Networks
The requirement for radio spectrum has been increasing and this has resulted in the materialization of wireless applications with enhanced features and higher data rate. The spectrum is scant, and the current radio spect...
Comparison of three types of physical aspects of a carbonated hydroxyapatite biomaterial: Study implantaion in vivo in rats of "Wistar" strain and physiological & physicochemical explorations
Currently, research on biomaterials must meet and demonstrate a set of therapeutic competence to level many health problems. The objective of our work is to normalize the technique of implantation of the biomaterial (car...
ACE gene polymorphism and serum ACE level with Progression of Nephropathy in Type 2 Diabetic Patients
Background. One of the most common complications of diabetes mellitus (DM) is diabetic nephropathy (DN). Â Angiotensin- converting enzyme (ACE) gene was the first candidate gene of renin-angiotensin system (RAS) for pred...