The checkpoint kinase ATM is centrally involved in the cellular response to DNA double-strand breaks. However, the mechanism of ATM activation during genotoxicstress is only partially understood. Here we report a direct regulatory linkage between the protein serine-threonine phosphatase 5 (PP5) and ATM. PP5 interacts with ATM in a DNA-damage-inducible manner. Reduced expression of PP5 attenuated DNA-damage-induced activation of ATM. Expression of a catalytically inactive PP5 mutant inhibited the phosphorylation of ATM substrates and the autophosphorylation of ATM on Ser 1981, and caused an S-phase checkpoint defect in DNA-damaged cells. Together our findings indicate that PP5 plays an essential role in the activation and checkpoint signaling functions of ATM in cells that have suffered DNA double-strand breaks.

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Repetitive transcranial magnetic stimulation is feasible and possibly efficacious in adolescents with MDD. In responders, rTMS may act by induced elevations in elevating DFPLC glutamate levels in the left DLPFC, thereby leading to symptom improvement.

Human orientation in novel and familiar environments is a complex skill that can involve numerous different strategies. To date, a comprehensive account of how these strategies interrelate at the behavioural level has not been documented, impeding the development of elaborate systems neuroscience models of spatial orientation. Here, we describe a virtual environment test battery designed to assess five of the core strategies used by humans to orient. Our results indicate that the ability to form a cognitive map is highly related to more basic orientation strategies, supporting previous proposals that encoding a cognitive map requires inputs from multiple domains of spatial processing. These findings provide a topology of numerous primary orientation strategies used by humans during orientation and will allow researchers to elaborate on neural models of spatial cognition that currently do not account for how different orientation strategies integrate over time based on environmental conditions.