Journal ArticleDOI
The Cdt1 protein is required to license DNA for replication in fission yeast.
TLDR
Genes related to Cdt1 have been found in Metazoa and plants, suggesting that the cooperation of Cdc6/Cdc18 with Cdt 1 to load MCM proteins onto chromatin may be a generally conserved feature of DNA licensing in eukaryotes.Abstract:
To maintain genome stability in eukaryotic cells, DNA is licensed for replication only after the cell has completed mitosis, ensuring that DNA synthesis (S phase) occurs once every cell cycle1. This licensing control is thought to require the protein Cdc6 (Cdc18 in fission yeast) as a mediator for association of minichromosome maintenance (MCM) proteins with chromatin2,3,4,5,6,7,8,9,10. The control is overridden in fission yeast by overexpressing Cdc18 (ref. 11) which leads to continued DNA synthesis in the absence of mitosis12. Other factors acting in this control have been postulated13 and we have used a re-replication assay to identify Cdt1 (ref. 14) as one such factor. Cdt1 cooperates with Cdc18 to promote DNA replication, interacts with Cdc18, is located in the nucleus, and its concentration peaks as cells finish mitosis and proceed to S phase. Both Cdc18 and Cdt1 are required to load the MCM protein Cdc21 onto chromatin at the end of mitosis and this is necessary to initiate DNA replication. Genes related to Cdt1 have been found in Metazoa and plants (A. Whitaker, I. Roysman and T. Orr-Weaver, personal communication), suggesting that the cooperation of Cdc6/Cdc18 with Cdt1 to load MCM proteins onto chromatin may be a generally conserved feature of DNA licensing in eukaryotes.read more
Citations
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Journal ArticleDOI
DNA replication in eukaryotic cells
Stephen P. Bell,Anindya Dutta +1 more
TL;DR: This review describes the current understanding of the events of initiation of eukaryotic replication factors and how they are coordinated with cell cycle progression and emphasizes recent progress in determining the function of the different replication factors once they have been assembled at the origin.
Journal ArticleDOI
Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression
Asako Sakaue-Sawano,Hiroshi Kurokawa,Toshifumi Morimura,Aki Hanyu,Hiroshi Hama,Hatsuki Osawa,Saori Kashiwagi,Kiyoko Fukami,Takaki Miyata,Hiroyuki Miyoshi,Takeshi Imamura,Masaharu Ogawa,Hisao Masai,Atsushi Miyawaki +13 more
TL;DR: Time-lapse imaging is performed to explore the spatiotemporal patterns of cell-cycle dynamics during the epithelial-mesenchymal transition of cultured cells, the migration and differentiation of neural progenitors in brain slices, and the development of tumors across blood vessels in live mice.
Journal ArticleDOI
Chromatin Association of Human Origin Recognition Complex, Cdc6, and Minichromosome Maintenance Proteins during the Cell Cycle: Assembly of Prereplication Complexes in Late Mitosis
Juan Méndez,Bruce Stillman +1 more
TL;DR: Using centrifugal elutriation of several human cell lines, it is demonstrated that whereas human Orc2 and hMcm proteins are present throughout the cell cycle, hCdc6p levels vary, being very low in early G1 and accumulating until cells enter mitosis, indicating that the mitotic kinase activity inhibits prereplication complex formation in human cells.
Journal ArticleDOI
Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.
James A. Wohlschlegel,Brian T. Dwyer,Suman Kumar Dhar,Christin Cvetic,Johannes C. Walter,Anindya Dutta +5 more
TL;DR: It is suggested that geminin inhibits inappropriate origin firing by targeting Cdt1, a recently identified replication initiation factor necessary for MCM loading in Multicellular eukaryotes.
Journal ArticleDOI
Preventing re-replication of chromosomal DNA
J. Julian Blow,Anindya Dutta +1 more
TL;DR: This work has shown that during late mitosis and G1, replication origins are 'licensed' for replication by loading the minichromosome maintenance (Mcm) 2–7 proteins to form a pre-replicative complex.
References
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Book ChapterDOI
Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
TL;DR: This chapter describes techniques concerned with classical and molecular genetics, cell biology, and biochemistry that can be used with Schizosaccharomyces pombe.
Journal ArticleDOI
Components and Dynamics of DNA Replication Complexes in S. cerevisiae: Redistribution of MCM Proteins and Cdc45p during S Phase
TL;DR: The results identify protein components of the pre-RC and a novel replication complex appearing at the G1/S transition (the RC), and suggest that after initiation MCM proteins and Cdc45p move with eukaryotic replication forks.
Journal ArticleDOI
A role for the nuclear envelope in controlling DNA replication within the cell cycle.
J. Julian Blow,Ronald A. Laskey +1 more
TL;DR: It is shown that nuclei replicated in vitro are unable to re-replicate in fresh replication extract until they have passed through mitosis, which suggests a simple model for the control of DNA replication in the cell cycle, whereby an essential replication factor is unable to cross the nuclear envelope but can only gain access to DNA when thenuclear envelope breaks down at mitosis.
Journal ArticleDOI
Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast
TL;DR: The Mcm proteins of budding yeast are abundant and are quantitatively found in a chromatin-enriched fraction specifically during the G1 phase of the cell cycle, providing evidence that a conserved biochemical pathway plays a critical role in coordinating DNA replication with mitosis in both yeast and higher eukaryotes.