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2014 (Vol. 5, Issue: 1)
Article Information:

The DNA Repair Key Enzyme Affected by 43Ca2+: A New Platform for Anti-Leukemia Therapies

Alexander A. Bukhvostov, Oleg A. Shatalov, Anatoly L. Buchachenko and Dmitry A. Kuznetsov
Corresponding Author:  Dmitry A. Kuznetsov 

Key words:  Acute Myeloblast Leukemia (AML), 40Ca and 43Ca isotopes, DNA polymerase Beta (DNApolB), Magnetic Isotope Effect (MIE), HL-60 cells, ,
Vol. 5 , (1): 42-48
Submitted Accepted Published
September 15, 2013 October 06, 2013 February 20, 2014
Abstract:

Human acute myeloblast leukemia HL60 cells over expresses a beta-type DNA polymerase (EC 2.7.7.7) which 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 isotopes mentioned are 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 prove the 43Ca-MIE dependent mode of the catalysis turning down. This 43Ca-promoted enzyme hyper-suppression leads to a residual synthesis of shorted DNA fragments that counts 25-35 nucleotides in length contrasting with the 180-210 n DNA produced by either intact or 40Ca-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 DNApol&beta was found over expressed. That confirms a concept considering the DNApol&beta 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 for molecular pharmacology of cancers is in a focus.
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  Cite this Reference:
Alexander A. Bukhvostov, Oleg A. Shatalov, Anatoly L. Buchachenko and Dmitry A. Kuznetsov , 2014. The DNA Repair Key Enzyme Affected by 43Ca2+: A New Platform for Anti-Leukemia Therapies.  British Journal of Pharmacology and Toxicology, 5(1): 42-48.
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