{"title":"Metabolic control of replisome plasticity in genome surveillance.","authors":"Mikkel Bo Petersen, Gita Chhetri, Kumar Somyajit","doi":"10.1016/j.tcb.2025.01.006","DOIUrl":null,"url":null,"abstract":"<p><p>Metabolic pathways and DNA replication are both adaptable and essential for early development and cancer progression. While each process is well understood individually, the mechanisms coordinating them are just beginning to emerge. Nucleotide biosynthesis serves as a crucial link, with fluctuating nucleotide pools leading to imbalanced deoxyribonucleotide (dNTP) and increased ribonucleotide (rNTP) levels, impairing DNA synthesis and triggering replication stress; ultimately driving developmental disorders and cancer. To counter these challenges, the replisome - the core machinery of DNA replication - continuously adjusts its architecture and speed in response to physiological changes, including nucleotide fluctuations. This review outlines recent insights into how the replisome aligns its function with metabolic changes in nucleotide levels and explores emerging links between metabolism and genome stability, and their roles in development and disease.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"880-892"},"PeriodicalIF":18.1000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tcb.2025.01.006","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Metabolic pathways and DNA replication are both adaptable and essential for early development and cancer progression. While each process is well understood individually, the mechanisms coordinating them are just beginning to emerge. Nucleotide biosynthesis serves as a crucial link, with fluctuating nucleotide pools leading to imbalanced deoxyribonucleotide (dNTP) and increased ribonucleotide (rNTP) levels, impairing DNA synthesis and triggering replication stress; ultimately driving developmental disorders and cancer. To counter these challenges, the replisome - the core machinery of DNA replication - continuously adjusts its architecture and speed in response to physiological changes, including nucleotide fluctuations. This review outlines recent insights into how the replisome aligns its function with metabolic changes in nucleotide levels and explores emerging links between metabolism and genome stability, and their roles in development and disease.
期刊介绍：
Trends in Cell Biology stands as a prominent review journal in molecular and cell biology. Monthly review articles track the current breadth and depth of research in cell biology, reporting on emerging developments and integrating various methods, disciplines, and principles. Beyond Reviews, the journal features Opinion articles that follow trends, offer innovative ideas, and provide insights into the implications of new developments, suggesting future directions. All articles are commissioned from leading scientists and undergo rigorous peer-review to ensure balance and accuracy.
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