Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast

Donovan, Shane; Harwood, Janet; Drury, Lucy S.; Diffley, John F.X.

doi:10.1073/pnas.94.11.5611

Cited by 479 publications

(463 citation statements)

References 55 publications

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“…In vitro studies show that after loading, Mcm2 -7 no longer requires ORC, Cdc6, or Cdt1 to associate with origin DNA (Donovan et al 1997;Randell et al 2006). Consistent with this observation, in vitro studies show that the helicase loading proteins are released from the origin upon Mcm2 -7 loading (Randell et al 2006;Tsakraklides and Bell 2010).…”

Section: Regulation and Dynamics Of Helicase Loadingsupporting

confidence: 66%

Helicase Loading at Chromosomal Origins of Replication

Bell

Kaguni

2013

Cold Spring Harbor Perspectives in Biology

120

109

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Loading of the replicative DNA helicase at origins of replication is of central importance in DNA replication. As the first of the replication fork proteins assemble at chromosomal origins of replication, the loaded helicase is required for the recruitment of the rest of the replication machinery. In this work, we review the current knowledge of helicase loading at Escherichia coli and eukaryotic origins of replication. In each case, this process requires both an origin recognition protein as well as one or more additional proteins. Comparison of these events shows intriguing similarities that suggest a similar underlying mechanism, as well as critical differences that likely reflect the distinct processes that regulate helicase loading in bacterial and eukaryotic cells.

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Section: Regulation and Dynamics Of Helicase Loadingsupporting

confidence: 66%

Helicase Loading at Chromosomal Origins of Replication

Bell

Kaguni

2013

Cold Spring Harbor Perspectives in Biology

120

109

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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%

“…In rapidly proliferating cells, pre-RCs are formed in late telophase and early G 1 well before entry into S phase. (22,(33)(34)(35)63) Therefore, all origins are licensed approximately at the same time and yet they are activated at different times during S phase. The mechanisms controlling the temporal activation of replication origins are not fully understood, but require the function of CDKs as well as Dbf4-dependent Cdc7 kinase (DDK), Rad53 and Mec1 kinases.…”

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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“…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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Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast

Cited by 479 publications

References 55 publications

Helicase Loading at Chromosomal Origins of Replication

Helicase Loading at Chromosomal Origins of Replication

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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