Regulating DNA Replication in Eukarya
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TLDR
Work from several organisms has revealed a conserved strategy whereby inactive replication complexes are assembled onto DNA during periods of low CDK and high APC activity but are competent to execute genome duplication only when these activities are reversed.Abstract:
DNA replication is tightly controlled in eukaryotic cells to ensure that an exact copy of the genetic material is inherited by both daughter cells. Oscillating waves of cyclin-dependent kinase (CDK) and anaphase-promoting complex/cyclosome (APC/C) activities provide a binary switch that permits the replication of each chromosome exactly once per cell cycle. Work from several organisms has revealed a conserved strategy whereby inactive replication complexes are assembled onto DNA during periods of low CDK and high APC activity but are competent to execute genome duplication only when these activities are reversed. Periods of high CDK and low APC/C serve an essential function by blocking reassembly of replication complexes, thereby preventing rereplication. Higher eukaryotes have evolved additional CDK-independent mechanisms for preventing rereplication.read more
Citations
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References
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Journal ArticleDOI
Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14.
TL;DR: It is found that Hct1 was phosphorylated in vivo at multiple CDK consensus sites during cell cycle stages when activity of the cyclin-dependent kinase Cdc28 is high and APC activity is low, and phosphorylation abolished the ability of HCT1 to activate the APC in vitro.
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Mitotic regulation of the human anaphase-promoting complex by phosphorylation.
Claudine Kraft,Franz Herzog,Christian Gieffers,Karl Mechtler,Anja Hagting,Jonathon Pines,Jan-Michael Peters +6 more
TL;DR: Immunofluorescence microscopy using phospho‐antibodies indicates that APC phosphorylation is initiated in prophase during nuclear uptake of cyclin B1, implying thatAPC activation is initiated by Cdk1 already in the nuclei of late prophase cells.
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Association of the Origin Recognition Complex with Heterochromatin and HP1 in Higher Eukaryotes
Daniel T.S. Pak,Michelle F. Pflumm,Igor Chesnokov,Da Wei Huang,Rebecca Kellum,Jacqueline Marr,Piotr Romanowski,Michael R. Botchan +7 more
TL;DR: The results indicate that ORC may play a widespread role in packaging chromosomal domains through interactions with heterochromatin-organizing factors and that heterozygous DmORC2 recessive lethal mutations resulted in a suppression of PEV.
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Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5.
Robertus A.M. de Bruin,W. Hayes McDonald,Tatyana I Kalashnikova,John R. Yates,Curt Wittenberg,Curt Wittenberg +5 more
TL;DR: Mutation of putative CDK phosphorylation sites, at least five of which are phosphorylated in vivo, strongly reduces SBF-dependent transcription and delays cell cycle initiation and, like mammalian Rb, Whi5 is a G1-specific transcriptional repressor antagonized by CDK.
Journal ArticleDOI
A p53-Dependent Checkpoint Pathway Prevents Rereplication
Cyrus Vaziri,Sandeep Saxena,Yesu Jeon,Yesu Jeon,Charles Lee,Kazutaka Murata,Yuichi J. Machida,Nikhil Wagle,Deog Su Hwang,Deog Su Hwang,Anindya Dutta +10 more
TL;DR: This work investigates how rereplication is prevented in normal mammalian cells and how these mechanisms might be overcome during tumor progression.