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

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

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements