DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in <i>Caenorhabditis elegans</i>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37590372.
- Also identified by DOI 10.1126/science.adi4932 and PMC identifier 7615117.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 <i>Caenorhabditis elegans</i> 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.
Medical subject headings
- Caenorhabditis elegans
- DNA Replication
- Minichromosome Maintenance Proteins
- Caenorhabditis elegans Proteins