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Unidirectional MCM translocation away from ORC drives origin licensing.
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 PDFReconstitution of human DNA licensing and the structural and functional analysis of key intermediates.
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.
View Article and Find Full Text PDFThe bioinformatics analysis and experimental validation of the carcinogenic role of EXO1 in lung adenocarcinoma.
Front Oncol
December 2024
Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Background: Exonuclease 1 (EXO1), a protein involved in mismatch repair and recombination processes, has been identified as a prognostic biomarker in lung adenocarcinoma (LUAD). Nevertheless, its role in LUAD progression remains elusive. This study seeks to elucidate the functional significance of EXO1 in LUAD and evaluate its potential as a therapeutic target.
View Article and Find Full Text PDFRNA Sequencing and Weighted Gene Co-Expression Network Analysis Highlight DNA Replication and Key Genes in Nucleolin-Depleted Hepatoblastoma Cells.
Genes (Basel)
November 2024
Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria.
Background/objectives: Nucleolin is a major component of the nucleolus and is involved in various aspects of ribosome biogenesis. However, it is also implicated in non-nucleolar functions such as cell cycle regulation and proliferation, linking it to various pathologic processes. The aim of this study was to use differential gene expression analysis and Weighted Gene Co-expression Network analysis (WGCNA) to identify nucleolin-related regulatory pathways and possible key genes as novel therapeutic targets for cancer, viral infections and other diseases.
View Article and Find Full Text PDFMCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis.
Nat Commun
January 2025
DNA Replication Group, Institute of Clinical Science, Imperial College London, London, UK.
The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled.
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