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Assembly of the CMG (CDC-45-MCM-2-7-GINS) helicase is the key regulated step during eukaryotic DNA replication initiation. Until now, it was unclear whether metazoa require additional factors that are not present in yeast. In this work, we show that Caenorhabditis elegans DNSN-1, the ortholog of human DONSON, functions during helicase assembly in a complex with MUS-101/TOPBP1. DNSN-1 is required to recruit the GINS complex to chromatin, and a cryo-electron microscopy structure indicates that DNSN-1 positions GINS on the MCM-2-7 helicase motor (comprising the six MCM-2 to MCM-7 proteins), by direct binding of DNSN-1 to GINS and MCM-3, using interfaces that we show are important for initiation and essential for viability. These findings identify DNSN-1 as a missing link in our understanding of DNA replication initiation, suggesting that initiation defects underlie the human disease syndrome that results from DONSON mutations.
Pubmed ID: 37590372
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Commercial organization which provides life science services and products to researchers. They specialize in gene synthesis, peptide, protein, antibody and preclinical drug development service.
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View all literature mentionsFocused on cell signalling pathways, provides access to reagents and services involving kinase and ubiquitin targets and associated substrates and interacting proteins. Provides expertise and assistance in projects development. Offers services for protein generation and antibody development.
View all literature mentionsMicrosoft system includes integrated digital inverted benchtop microscope for four-color fluorescence, transmitted-light, and color imaging. Provides interchangeable optics with autofocus, single-click multi-channel image acquisition.3.2 Megapixels, monochrome, CMOS camera. Offers software for acquisition, analysis, and automated cell counting.
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The data sets included in this resource are published in Kravitz et al, 2012. Distinct roles for direct and indirect pathway striatal neurons in reinforcement (Nat. Neurosci).
