Loss of ATM kinase activity leads to embryonic lethality in mice

Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, a cancer-prone neurodegenerative disease, present with null mutations in Atm. To determine whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate-ribose) polymerase inhibition and increased genomic instability. These results may explain why missense mutations with no detectable kinase activity are rarely found in patients with classical A-T. We propose that ATM kinase-inactive missense mutations, unless otherwise compensated for, interfere with HR during embryogenesis

Chemical Oxidative Kinetic Study of Arsenopyrite Dissolved by Iron Solution

To extract the Au efficiently, the kinetic experiments were performed in a 1000 mL-glass bulbs which were made by us to determine the oxidative dissolution of arsenopyrite by iron solution. The results show that the rate of dissolution of arsenopyrite increases with the increasing of temperature from 30 degrees C to 75 degrees C, in which an apparent activation energy for arsenopyrite oxidation is 10.850 kJ.mol(-1). Moreover, the rate of oxidative dissolution of arsenopyrite increases with the increasing of concentration of ferric iron with the reaction order is 0.34 (4.62 similar to 40.04 g.L-1) and 0.61 (27.32 similar to 36.33 g.L-1). In contrast, the reduction of hydrogen ion can promote concentration promotes the leaching rate of arsenopyrite with the reaction order of -0.29