The full licensing of replication origins in late G1 is normally enforced by the licensing checkpoint. In this issue, Matson et al. (2019. https://doi.org/10.1083/jcb.201902143) show that this checkpoint is inoperative in cells exiting from G0, resulting in incomplete origin licensing and consequent replicative stress.
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http://dx.doi.org/10.1083/jcb.201905181 | DOI Listing |
Nat Commun
January 2025
Macromolecular Machines Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
The MCM motor of the eukaryotic replicative helicase is loaded as a double hexamer onto DNA by the Origin Recognition Complex (ORC), Cdc6, and Cdt1. ATP binding supports formation of the ORC-Cdc6-Cdt1-MCM (OCCM) helicase-recruitment complex where ORC-Cdc6 and one MCM hexamer form two juxtaposed rings around duplex DNA. ATP hydrolysis by MCM completes MCM loading but the mechanism is unknown.
View Article and Find Full Text PDFJ Headache Pain
January 2025
Sensory Biology Unit, Translational Research Center, Rigshospitalet, Glostrup, Denmark.
Objective: The neuropeptide calcitonin gene-related peptide (CGRP) has been established to be a key signaling molecule in migraine, but little is known about the differences between the two isoforms: αCGRP and βCGRP. Previous studies have been hampered by their close similarity, making the development of specific antibodies nearly impossible. In this study we sought to test the hypothesis that αCGRP and βCGRP localize differently within the neurons of the mouse trigeminal ganglion (TG), using αCGRP knock out (KO) animals.
View Article and Find Full Text PDFMediastinum
November 2024
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Background: Thymoma is a rare mediastinal neoplasm originating from thymic epithelial cells, often associated with paraneoplastic syndromes. These syndromes can manifest as a range of autoimmune disorders, including myasthenia gravis, pure red cell aplasia, and aplastic anemia. Clinical trials involving the use of immune checkpoint inhibitors (ICIs) in thymoma have been complicated by a high incidence of immune-related adverse effects (irAEs).
View Article and Find Full Text PDFBMC Plant Biol
January 2025
Triticeae Research Institute, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.
Background: The St-genome-sharing taxa are highly complex group of the species with the St nuclear genome and monophyletic origin in maternal lineages within the Triticeae, which contains more than half of polyploid species that distributed in a wide range of ecological habitats. While high level of genetic heterogeneity in plastome DNA due to a reticulate evolutionary event has been considered to link with the richness of the St-genome-sharing taxa, the relationship between the dynamics of diversification and molecular evolution is lack of understanding.
Results: Here, integrating 106 previously and 12 newly sequenced plastomes representing almost all previously recognized genomic types and genus of the Triticeae, this study applies phylogenetic reconstruction methods in combination with lineage diversification analyses, estimate of sequence evolution, and gene expression to investigate the dynamics of diversification in the tribe.
Nat Commun
January 2025
DNA Replication Group, Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase that unwinds DNA during S-phase. Here, we report the reconstitution of human DNA licensing using purified proteins.
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