Probing the Mec1ATR Checkpoint Activation Mechanism with Small Peptides.

The dimeric architecture of checkpoint Mec1ATR and Tel1ATM reveal a common structural organization

PP2A Controls Genome Integrity by Integrating Nutrient-Sensing and Metabolic Pathways with the DNA Damage Response

Mec1ATR mediates the DNA damage response (DDR), integrating chromosomal signals and mechanical stimuli. We show that the PP2A phosphatases, ceramide-activated enzymes, couple cell metabolism with the DDR. Using genomic screens, metabolic analysis, and genetic and pharmacological studies, we found that PP2A attenuates the DDR and that three metabolic circuits influence the DDR by modulating PP2A...

Effects of the sintering temperature on the flux-pinning mechanism and the activation energy of malic-acid doped MgB2

  The flux-pinning mechanism and activation energy of 10 wt % malic acid-doped MgB2 were investigated by measuring of the critical current density and resistivity as a function of magnetic field and temperature. A crossover field, Bsb, was observed from the single vortex to the small vortex bundle pinning regime. For the sintered sample, the temperature dependence of Bsb(T) at low temperature i...

The unstructured C-terminal tail of the 9-1-1 clamp subunit Ddc1 activates Mec1/ATR via two distinct mechanisms.

DNA damage checkpoint pathways operate to prevent cell-cycle progression in response to DNA damage and replication stress. In S. cerevisiae, Mec1-Ddc2 (human ATR-ATRIP) is the principal checkpoint protein kinase. Biochemical studies have identified two factors, the 9-1-1 checkpoint clamp and the Dpb11/TopBP1 replication protein, as potential activators of Mec1/ATR. Here, we show that G1 phase c...

Dendritic Cell Immunotherapy, the Next Step in Cancer Treatment

Cancer immunotherapy has gained a lot of interest over the past few years due to the success of immune checkpoint inhibitors in treating cancer (1, 2). Immune checkpoint inhibitors, such as monoclonal antibodies against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), have been shown to increase survival of patients with advanced cancers (1, 2). These in...