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Yeast Mec1, and its mammalian ortholog, Ataxia-Telangiectasia and Rad3-related, are giant protein kinases central to replication stress and double strand DNA break repair. Mec1, in complex with Ddc2, is a 'sensor' of single stranded DNA, and phosphorylates numerous cell cycle and DNA repair factors to enforce cell cycle arrest and facilitate repair. Over the last several years, new techniques - particularly in structural biology - have provided molecular mechanisms for Mec1 function. It is becoming increasingly clear how post-translational modification of Mec1 and its interaction partners modulates the DNA damage checkpoint. In this review, we summarise the most recent work unravelling Mec1 function in the DNA damage checkpoint and provide a molecular context for its regulation by phosphorylation.
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http://dx.doi.org/10.1016/j.dnarep.2023.103543 | DOI Listing |
Nat Metab
September 2025
Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, Braunschweig, Germany.
Itaconate is an immunomodulatory metabolite that alters mitochondrial metabolism and immune cell function. This organic acid is endogenously synthesized by tricarboxylic acid (TCA) metabolism downstream of TLR signalling. Itaconate-based treatment strategies are under investigation to mitigate numerous inflammatory conditions.
View Article and Find Full Text PDFLeukemia
September 2025
University Children's Hospital Zurich, Pediatric Oncology and Children's Research Center, Zurich, Switzerland.
Acute lymphoblastic leukemia (ALL) preferentially localizes in the bone marrow (BM) and displays recurrent patterns of medullary and extra-medullary involvement. Leukemic cells exploit their niche for propagation and survive selective pressure by chemotherapy in the BM microenvironment, suggesting the existence of protective mechanisms. Here, we established a three-dimensional (3D) BM mimic with human mesenchymal stromal cells and endothelial cells that resemble vasculature-like structures to explore the interdependence of leukemic cells with their microenvironment.
View Article and Find Full Text PDFLeukemia
September 2025
I.R.C.C.S Santa Lucia Foundation, Via del Fosso di Fiorano, Rome, Italy.
At present there is no metabolic characterization of acute promyelocytic leukemia (APL). Pathognomonic of APL, PML::RARα fusion protein rewires metabolic pathways to feed anabolic tumor cell's growth. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapies render APL the most curable subtype of AML, yet approximately 1% of cases are resistant and 5% relapse.
View Article and Find Full Text PDFeNeuro
September 2025
Department of Neurobiology and McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL35294 and.
The plasma membrane acts as a capacitor that plays a critical role in neuronal excitability and signal propagation. Neuronal capacitance is proportional to the area of the cell membrane, thus is often used as a measure of cell size that is assumed to be relatively stable. Recent work proposes that the capacitance of dentate granule cells and cortical pyramidal cells changes across the light-dark cycle in a manner that alters synaptic integration.
View Article and Find Full Text PDFGenome Res
September 2025
College of Life Science, Sichuan Agricultural University, Ya'an, 625014, People's Republic of China;
Poultry egg production is shaped by the intertwined action of multiple physiological systems, greatly magnifying the complexity of its underlying genetic regulation. Although multitissue mapping of regulatory variants offers a powerful route to untangle this complexity, comprehensive data sets in ducks remain scarce. Meanwhile, the contributions of peripheral systems beyond neuroendocrine regulation on poultry egg production are still largely unexplored.
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