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dc.contributor.authorKanemaki, Masato
dc.contributor.authorLabib, Karim
dc.date.accessioned2009-07-07T12:13:54Z
dc.date.available2009-07-07T12:13:54Z
dc.date.issued2006-04-19
dc.identifier.citationDistinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks. 2006, 25 (8):1753-63 EMBO J.en
dc.identifier.issn0261-4189
dc.identifier.pmid16601689
dc.identifier.doi10.1038/sj.emboj.7601063
dc.identifier.urihttp://hdl.handle.net/10541/72796
dc.description.abstractThe Cdc45 protein is crucial for the initiation of chromosome replication in eukaryotic cells, as it allows the activation of prereplication complexes (pre-RCs) that contain the MCM helicase. This causes the unwinding of origins and the establishment of DNA replication forks. The incorporation of Cdc45 at nascent forks is a highly regulated and poorly understood process that requires, in budding yeast, the Sld3 protein and the GINS complex. Previous studies suggested that Sld3 is also important for the progression of DNA replication forks after the initiation step, as are Cdc45 and GINS. In contrast, we show here that Sld3 does not move with DNA replication forks and only associates with MCM in an unstable manner before initiation. After the establishment of DNA replication forks from early origins, Sld3 is no longer essential for the completion of chromosome replication. Unlike Sld3, GINS is not required for the initial recruitment of Cdc45 to origins and instead is necessary for stable engagement of Cdc45 with the nascent replisome. Like Cdc45, GINS then associates stably with MCM during S-phase.
dc.language.isoenen
dc.subject.meshCell Cycle Proteins
dc.subject.meshChromosomes, Fungal
dc.subject.meshDNA Helicases
dc.subject.meshDNA Replication
dc.subject.meshDNA-Binding Proteins
dc.subject.meshNuclear Proteins
dc.subject.meshReplication Origin
dc.subject.meshSaccharomyces cerevisiae
dc.subject.meshSaccharomyces cerevisiae Proteins
dc.titleDistinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK.en
dc.identifier.journalThe EMBO Journalen
html.description.abstractThe Cdc45 protein is crucial for the initiation of chromosome replication in eukaryotic cells, as it allows the activation of prereplication complexes (pre-RCs) that contain the MCM helicase. This causes the unwinding of origins and the establishment of DNA replication forks. The incorporation of Cdc45 at nascent forks is a highly regulated and poorly understood process that requires, in budding yeast, the Sld3 protein and the GINS complex. Previous studies suggested that Sld3 is also important for the progression of DNA replication forks after the initiation step, as are Cdc45 and GINS. In contrast, we show here that Sld3 does not move with DNA replication forks and only associates with MCM in an unstable manner before initiation. After the establishment of DNA replication forks from early origins, Sld3 is no longer essential for the completion of chromosome replication. Unlike Sld3, GINS is not required for the initial recruitment of Cdc45 to origins and instead is necessary for stable engagement of Cdc45 with the nascent replisome. Like Cdc45, GINS then associates stably with MCM during S-phase.


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