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 OF ADVANCES IN CHEMISTRY
View Publication Info| Field | Value | |
| Title |
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
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| Creator |
Shatalov, Oleg A.
Grigoryev, Maxim E. Bukhvostov, Alexander A. Kuznetsov, Dmitry A. |
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| Subject |
Chemistry / Biochemistry
magnetic isotope effect; nuclear spin selectivity; DNArepair; 40Ca and 43Ca isotopes; ion-radical path in the metal – dependent enzymatic catalysis |
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| Description |
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-invalid”) 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.
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| Publisher |
CIRWORLD
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| Date |
2008-12-12
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| Type |
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion Peer-reviewed Article Research Paper (Experimental Study) |
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| Format |
application/pdf
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| Identifier |
http://cirworld.com/index.php/jac/article/view/953
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| Source |
JOURNAL OF ADVANCES IN CHEMISTRY; Vol 4 No 3; 554-562
2321-807X |
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| Language |
eng
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| Relation |
http://cirworld.com/index.php/jac/article/view/953/932
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| Rights |
Copyright (c) 2016 JOURNAL OF ADVANCES IN CHEMISTRY
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