An essential role for the Cdc6 protein in forming the pre-replicative complexes of budding yeast

Cocker, Julie H.; Piatti, Simonetta; Santocanale, Corrado; Nasmyth, Kim; Diffley, John F.X.

doi:10.1038/379180a0

Cited by 336 publications

(279 citation statements)

References 24 publications

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“…Instead, this Cdk activity may be associated with preparative events for the next cell cycle. It is well established that the preliminary events of S phase occur in late mitosis (for example see Cocker et al, 1996). Deletion of SPO12 and SIC1 both lead to a slight protraction of M phase (Donovan et al, 1994;Parkes and Johnston, 1992) and perhaps, in the absence of Pho85, defects occur in the M-G1 transition leading to the observed temperature sensitivity in the double mutants.…”

Section: Discussionmentioning

confidence: 99%

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Swi5 Controls a Novel Wave of Cyclin Synthesis in Late Mitosis

Aerne¹,

Johnson²,

Toyn³

et al. 1998

MBoC

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We have shown previously that the Swi5 transcription factor regulates the expression of the SIC1 Cdk inhibitor in late mitosis. This suggests that Swi5 might control other genes with roles in ending mitosis. We identified a gene with a Swi5-binding site in the promoter that encoded a protein with high homology to Pcl2, a cyclin-like protein that associates with the Cdk Pho85. This gene, PCL9, is indeed regulated by Swi5 in late M phase, the only cyclin known to be expressed at this point in the cell cycle. The Pcl9 protein is associated with a Pho85-dependent protein kinase activity, and the protein is unstable with peak levels occurring in late M phase. PCL2 is already known to be expressed in late G1 and we find that, in addition, it is also regulated by Swi5 in telophase. The expression of PCL2 and PCL9 at this stage of the cell cycle implies a role for the Pho85 Cdk at the end of mitosis. Consistent with this a synthetic interaction was observed between pho85⌬ and strains deleted for SIC1, SWI5, and SPO12. These and other studies support the notion that the M/G1 switch is a major cell cycle transition.

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Section: Discussionmentioning

confidence: 99%

“…In the case of CDC6, this is likely to be due to its essential role in establishing the prereplication complex (pre-RC) that normally occurs in late M phase (Cocker et al, 1996). In stationary phase, this pre-RC is lost and then needs to be reformed in G1 for the initial cell cycle after refeeding.…”

Section: Discussionmentioning

confidence: 99%

Swi5 Controls a Novel Wave of Cyclin Synthesis in Late Mitosis

Aerne¹,

Johnson²,

Toyn³

et al. 1998

MBoC

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“…(30) Its participation in initiation of DNA replication has been confirmed genetically and biochemically. (31)(32)(33)(34)(35) Cdc6 can associate with ORC in vitro and influence its sensitivity to proteases, suggesting an induced structural change. (36) In addition, the ATP-binding domain of Cdc6 is essential for pre-RC assembly (see below; Refs.…”

Section: Introductionmentioning

confidence: 99%

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

2003

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SummaryThe hardest part of replicating a genome is the beginning. The first step of DNA replication (called ''initiation'') mobilizes a large number of specialized proteins (''initiators'') that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ringshaped helicase onto the DNA double helix.

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“…The loading of Cdc6 onto chromatin is a critical step in the formation of a pre-RC (Liang et al, 1995;Cocker et al, 1996;Detweiler and Li, 1997). Thus, because Cdc6* reloads prematurely, strains expressing Cdc6* might be prone to rereplication.…”

Section: Cdc6*-nls Is Toxic and Causes Rereplication In Orc2* Orc6* Smentioning

confidence: 99%

“…In the yeast Saccharomyces cerevisiae, but also in many other organisms, the binding of Cdc6 to the origin recognition complex (ORC) is a critical step in the formation of pre-RCs (Liang et al, 1995;Cocker et al, 1996;Detweiler and Li, 1997) and essential for subsequent loading of Mcm proteins (Mcm2-7; Piatti et al, 1996;Santocanale and Diffley, 1996;Aparicio et al, 1997;Donovan et al, 1997;Tanaka et al, 1997). After licensing the origin by loading Mcms, endogenous Cdc6 dissociates from the replicative complex and only reassociates with chromatin late in M-phase Weinreich et al, 1999) when cyclin-dependent protein kinase (Clb-Cdc28) activities are absent.…”

Section: Introductionmentioning

confidence: 99%

Roles of the CDK Phosphorylation Sites of Yeast Cdc6 in Chromatin Binding and Rereplication

Honey

Futcher

2007

MBoC

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The Saccharomyces cerevisiae Cdc6 protein is crucial for DNA replication. In the absence of cyclin-dependent kinase (CDK) activity, Cdc6 binds to replication origins, and loads Mcm proteins. In the presence of CDK activity, Cdc6 does not bind to origins, and this helps prevent rereplication. CDK activity affects Cdc6 function by multiple mechanisms: CDK activity affects transcription of CDC6, degradation of Cdc6, nuclear import of Cdc6, and binding of Cdc6 to Clb2. Here we examine some of these mechanisms individually. We find that when Cdc6 is forced into the nucleus during late G1 or S, it will not substantially reload onto chromatin no matter whether its CDK sites are present or not. In contrast, at a G2/M nocodazole arrest, Cdc6 will reload onto chromatin if and only if its CDK sites have been removed. Trace amounts of nonphosphorylatable Cdc6 are dominant lethal in strains bearing nonphosphorylatable Orc2 and Orc6, apparently because of rereplication. This synthetic dominant lethality occurs even in strains with wild-type MCM genes. Nonphosphorylatable Cdc6, or Orc2 and Orc6, sensitize cells to rereplication caused by overexpression of various replication initiation proteins such as Dpb11 and Sld2.

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An essential role for the Cdc6 protein in forming the pre-replicative complexes of budding yeast

Cited by 336 publications

References 24 publications

Swi5 Controls a Novel Wave of Cyclin Synthesis in Late Mitosis

Swi5 Controls a Novel Wave of Cyclin Synthesis in Late Mitosis

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

Roles of the CDK Phosphorylation Sites of Yeast Cdc6 in Chromatin Binding and Rereplication

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