期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：47
页码：13390-13395
DOI：10.1073/pnas.1613825113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceFor DNA to be duplicated, it must first be unwound. Here, we examine the nature of the helicase engine that drives this unwinding process. In archaea and eukaryotes, the core helicase is the MCM complex. Our studies reveal that the active form of the archaeal replicative helicase is a complex of MCM with the accessory proteins Cdc45 and GINS. Our work reveals functional conservation of this architecture despite the 2 billion-year evolutionary gulf between archaea and eukaryotes. The regulated recruitment of Cdc45 and GINS is key to activating the eukaryotic MCM(2-7) replicative helicase. We demonstrate that the homohexameric archaeal MCM helicase associates with orthologs of GINS and Cdc45 in vivo and in vitro. Association of these factors with MCM robustly stimulates the MCM helicase activity. In contrast to the situation in eukaryotes, archaeal Cdc45 and GINS form an extremely stable complex before binding MCM. Further, the archaeal GINS[bullet]Cdc45 complex contains two copies of Cdc45. Our analyses give insight into the function and evolution of the conserved core of the archaeal/eukaryotic replisome.
