High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Stochastic association of neighboring replicons creates replication factories in budding yeast

Peer reviewedPublisher PD

Calmodulin-dependent protein kinase kinase-beta activates AMPK without forming a stable complex:synergistic effects of Ca2+ and AMP

Activation of AMPK (AMP-activated protein kinase) by phosphorylation at Thr172 is catalysed by at least two distinct upstream kinases, i.e. the tumour suppressor LKB1, and CaMKKβ (Ca2+/calmodulin-dependent protein kinase kinase-β). The sequence around Thr172 is highly conserved between the two catalytic subunit isoforms of AMPK and the 12 AMPK-related kinases, and LKB1 has been shown to act upstream of all of them. In the present paper we report that none of the AMPK-related kinases tested could be phosphorylated or activated in intact cells or cell-free assays by CaMKKβ, although we did observe a slow phosphorylation and activation of BRSK1 (brain-specific kinase 1) by CaMKKα. Despite recent reports, we could not find any evidence that the α and/or β subunits of AMPK formed a stable complex with CaMKKβ. We also showed that increasing AMP concentrations in HeLa cells (which lack LKB1) had no effect on basal AMPK phosphorylation, but enhanced the ability of agents that increase intracellular Ca2+ to activate AMPK. This is consistent with the effect of AMP on phosphorylation of Thr172 being due to inhibition of dephosphorylation, and confirms that the effect of AMP is independent of the upstream kinase utilized

The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice

Background The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations