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CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair.
Nat Commun
January 2025
Robson DNA Science Centre, Charbonneau Cancer Institute, Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.
View Article and Find Full Text PDFA promising future for breast cancer therapy with hydroxamic acid-based histone deacetylase inhibitors.
Bioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFNew physiological insights using multi-TE ASL MRI measuring blood-brain barrier water exchange after caffeine intake.
MAGMA
January 2025
Imaging Physics, Fraunhofer Institute for Digital Medicine MEVIS, Max-von-Laue-Straße 2, 28359, Bremen, Germany.
Objectives: Caffeine, a known neurostimulant and adenosine antagonist, affects brain physiology by decreasing cerebral blood flow. It interacts with adenosine receptors to induce vasoconstriction, potentially disrupting brain homeostasis. However, the impact of caffeine on blood-brain barrier (BBB) permeability to water remains underexplored.
View Article and Find Full Text PDFAdvances in Protein Kinase Regulation of Stress Responses in Fruits and Vegetables.
Int J Mol Sci
January 2025
Integrative Agriculture Department, College of Agriculture and Veterinary Medicine, United Arab Emirates University, Al Ain 15551, United Arab Emirates.
Fruits and vegetables (F&Vs) are essential in daily life and industrial production. These perishable produces are vulnerable to various biotic and abiotic stresses during their growth, postharvest storage, and handling. As the fruit detaches from the plant, these stresses become more intense.
View Article and Find Full Text PDFAn Addendum to the Chemiosmotic Theory of Mitochondrial Activity: The Role of RNA as a Proton Sink.
Biomolecules
January 2025
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Mitochondrial ATP synthesis is driven by harnessing the electrochemical gradient of protons (proton motive force) across the mitochondrial inner membrane via the process of chemiosmosis. While there is consensus that the proton gradient is generated by components of the electron transport chain, the mechanism by which protons are supplied to ATP synthase remains controversial. As opposed to a global coupling model whereby protons diffuse into the intermembrane space, a localised coupling model predicts that protons remain closely associated with the lipid membrane prior to interaction with ATP synthase.
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