{"title":"How similar are the molecular mechanisms of yeast and metazoan genome replication initiation?","authors":"Giacomo Palm, Alessandro Costa","doi":"10.1042/BST20220917","DOIUrl":null,"url":null,"abstract":"<p><p>DNA replication start sites are licensed for replication when two hexameric ring-shaped motors of the replicative helicase are loaded as an inactive double hexamer around duplex DNA. Activation requires untwisting of the double helix and ejection of one DNA strand from the central channel of each helicase ring. The process of replication initiation is best understood in yeast, thanks to reconstitution with purified yeast proteins, which allowed systematic structural analysis of the replication initiation process. Orthologs of most yeast replication factors have been identified in higher eukaryotes; however, reconstitution of metazoan replication initiation is still in its infancy, with double hexamer loading but not activation having been achieved. Nonetheless, artificial intelligence-driven structure prediction and cryo-EM studies on native complexes, combined with cell-based and cell-free approaches, are starting to provide insights into metazoan replication initiation mechanisms. Here, we describe the emerging picture.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 2","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical Society transactions","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1042/BST20220917","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
DNA replication start sites are licensed for replication when two hexameric ring-shaped motors of the replicative helicase are loaded as an inactive double hexamer around duplex DNA. Activation requires untwisting of the double helix and ejection of one DNA strand from the central channel of each helicase ring. The process of replication initiation is best understood in yeast, thanks to reconstitution with purified yeast proteins, which allowed systematic structural analysis of the replication initiation process. Orthologs of most yeast replication factors have been identified in higher eukaryotes; however, reconstitution of metazoan replication initiation is still in its infancy, with double hexamer loading but not activation having been achieved. Nonetheless, artificial intelligence-driven structure prediction and cryo-EM studies on native complexes, combined with cell-based and cell-free approaches, are starting to provide insights into metazoan replication initiation mechanisms. Here, we describe the emerging picture.
期刊介绍:
Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences.
Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.