Cell cycle control of replication initiation in eukaryotes

doi:10.1016/S0955-0674(96)80082-2

Current Opinion in Cell Biology

Volume 8, Issue 6, December 1996, Pages 815-821

https://doi.org/10.1016/S0955-0674(96)80082-2 Get rights and content

Abstract

Studies on the initiation of DNA replication in eukaryotes have progressed recently through different approaches that promise to converge. Proteins interacting with the origin recognition complex form a prereplicative complex early in the cell cycle. The regulation of the binding of MCM/P1 proteins to chromatin plays a key role in the replication licensing system which prevents re-replication in a single cell cycle. Cyclin-dependent kinases provide an overall control of the cell cycle by stimulating S-phase entry and possibly by preventing re-establishment of prereplicative complexes in G₂ phase.

References (67)

KA Gavin et al.
Conserved initiator proteins in eukaryotes
Science
(1995)
M Muzi-Falconi et al.
Orp1, a member of the Cdc18/Cdc6 family of S-phase regulators, is homologous to a component of the origin recognition complex
Proc Natl Acad Sci USA
(1995)
S Piatti et al.
Cdc6 is an unstable protein whose de novo synthesis in G(1) is important for the onset of S phase and for preventing a reductional anaphase in the budding yeast Saccharomyces cerevisiae
EMBO J
(1995)
AL Jackson et al.
Cell cycle regulation of the yeast Cdc7 protein-kinase by association with the Dbf4 protein
Mol Cell Biol
(1993)
SE Kearsey et al.
Cell cycle control of eukaryotic DNA replication
Curr Opin Genet Dev
(1996)
H Kimura et al.
DNA polymerase alpha associated protein P1, murine homolog of yeast MCM3, changes its intranuclear distribution during the DNA synthetic period
EMBO J
(1994)
IT Todorov et al.
BM28, a human member of the MCM2-3-5 family, is displaced from chromatin during DNA replication
J Cell Biol
(1995)
M Coue et al.
Chromatin binding, nuclear localization and phosphorylation of Xenopus Cdc21 are cell cycle dependent and associated with the control of initiation of DNA replication
EMBO J
(1996)
H Zhang et al.
p19(Skp1) and p45(Skp2) are essential elements of the cyclin A-Cdk2 S phase kinase
Cell
(1995)
J Hayles et al.
Temporal order of S phase and mitosis in fission yeast is determined by the state of the p34cdc2-mitotic B cyclin complex
Cell
(1994)

PV Jallepalli et al.

Rum1 and Cdc18 link inhibition of cyclin-dependent kinase to the initiation of DNA replication in Schizosaccharmyces pombe

Genes Dev

(1996)

C Dahmann et al.

S phase promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state

Curr Biol

(1995)

S Donovan et al.

Replication origins in eukaroytes

Curr Opin Genet Dev

(1996)

S Loo et al.

The origin recognition complex in silencing, cell cycle progression and DNA replication

Mol Biol Cell

(1995)

CA Fox et al.

The origin recognition complex has essential functions in transcriptional silencing and chromosomal replication

Genes Dev

(1995)

C Liang et al.

ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome

Cell

(1995)

SP Bell et al.

The multidomain structure of Orc1p reveals similary to regulators of DNA replication and transcriptional silencing

Cell

(1995)

M Gossen et al.

A Drosophila homolog of the yeast origin recognition complex

Science

(1995)

PB Carpenter et al.

Role for a Xenopus Orc2-related protein in controlling DNA replication

Nature

(1996)

J Leatherwood et al.

Interaction of cdc2 and cdc18 with a fission yeast orc2-like protein

Nature

(1996)

K Takahara et al.

Mouse and human homologues of the yeast origin of replication recognition complex subunit ORC2 and chromosomal localization of the cognate human gene ORC2L

Genomics

(1996)

A Rowles et al.

Interaction between the origin recognition complex and the replication licensing system in Xenopus

Cell

(1996)

S Chevalier et al.

Overview of the regulation of S phase in Xenopus egg extracts

Biochimie

(1995)

P Thommes et al.

The DNA replication licensing system

Cancer Surveys

(1996)

JFX Diffley et al.

Stepwise assembly of initiation-complexes at budding yeast replication origins during the cell-cycle

J Cell Sci

(1995)

H Nishitani et al.

P65(Cdc18) plays a major role controlling the initiation of DNA replication in fission yeast

Cell

(1995)

M Muzi-Falconi et al.

Cdc18(+) regulates initiation of DNA replication in Schizosaccharomyces pombe

Proc Natl Acad Sci USA

(1996)

JH Cocker et al.

An essential role for the cdc6 protein in forming the pre-replicative complexes of budding yeast

Nature

(1996)

SJ Dowell et al.

Interaction of Dbf4, the Cdc7 protein-kinase requlatory subunit, with yeast replication origins in vivo

Science

(1994)

H Masai et al.

Hsk1(+), a Schizosaccharomyces pombe gene related to Saccharomyces cerevisiae Cdc7, is required for chromosomal replication

EMBO J

(1995)

JPJ Chong et al.

The role of MCM/P1 proteins in the licensing of DNA replication

Trends Biochem Sci

(1996)

JPJ Chong et al.

Purification of an Mcm-containing complex as a component of the DNA replication licensing system

Nature

(1995)

Y Kubota et al.

Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor

Cell

(1995)

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Initiation of nuclear DNA replication begins when a prereplication complex (preRC) is assembled at sites distributed throughout the nuclear genome. This event, termed “origin licensing” (Chevalier & Blow, 1996), occurs as cells transit from anaphase in mitosis to G1 phase of the mitotic cell division cycle (Fig. 2) (Baldinger & Gossen, 2009; Noguchi, Vassilev, Ghosh, Yates, & DePamphilis, 2006). Thus, preRC assembly also is referred to as “origin licensing” because it permits replication origins to initiate DNA synthesis.
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Unexpectedly, among the 24 proteins whose expression was found to be regulated by chronic high glucose exposure, we found the 6 MCM2-7 helicases composing the entire eukaryotic MCM complex. This latter constitute the core of the pre-replication complex required for DNA synthesis during S-phase, together with the cyclin-dependent kinases (CDKs), the Origin Recognition Complex (ORC), and Cdc6/18 proteins [31,32]. The 6 proteins of the MCM complex were found up-regulated in the nucleus of β-cells exposed to chronic high glucose concentration, together with the kinases cdk1 and cdk2, which are two key actors of the G1/S transition.
Proper functioning of pancreatic β-cells is a crucial for glucose homeostasis control, and therefore a main problem regarding type 2 diabetes onset and evolution. The ability of β-cells to proliferate upon certain stimuli, such as elevated glucose concentration, is an essential property to overpass a major problem of the pathology: the decrease of β-cell mass leading to a lack of insulin production. However, high glucose concentrations are also an inducer of β-cell dysfunction, when proliferation become unable to overcome insulin demand. The control of β-cell proliferation could represent an interesting target for the development of therapeutic molecules for type 2 diabetes treatment. To get new insights on β-cell replication, we investigated the modulation of nuclear proteins of INS-1E cells submitted to medium and high glucose concentrations for 24 h. Indeed, the nucleus should contain proteins responsible of proliferation-related events. The SILAC approach allowed us identifying 24 nuclear proteins whose expressions were modified by chronic high glucose. A wide Downstream Effects Analysis assigned the majority of the differentially expressed proteins to functions such as proliferation and cell cycle. Interestingly, our study linked for the first time the increase of expression of the 6 MCM components to glucose-induced stimulation in β-cells.
The current study represents a progress in the understanding of glucose-induced proliferation mechanisms in β-cells. We applied the SILAC strategy to INS-1E cells cultivated with medium or high glucose concentrations for 24 h, and we targeted nuclear proteins which have a central role in proliferation-related mechanisms. It allows quantifying 24 nuclear proteins, which are regulated by high glucose exposure. The vast majority of them are shown to be related to proliferation and cell cycle. We describe here for the first time than the 6 proteins of the MCM complex are involved in glucose-mediated proliferation in β-cells.
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The proliferative capacity of tumor cells is a characteristic feature in the whole growing tumors. Many pathologists and clinicians have used the estimation of cell proliferation for prognostic information. Minichromosome maintenance protein 3 (MCM3) is known to have a role on the initiation and regulation of DNA replication during cell cycle. The aim of this study was to evaluate the potential applicability of one of the MCM proteins, MCM3, as a proliferation marker in papillary thyroid carcinoma (PTC) with correlation to clinicopathological parameters. We performed the immunohistochemical analysis for MCM3 and Ki-67 in 60 cases of PTC and Western blot analysis for MCM3 expression in 6 PTCs and normal thyroid tissues. The comparison of MCM3 labeling index (LI) to tumor size (P = 0.031) and extrathyroidal extension (P = 0.037) was statistically significant while that of Ki-67 LI to them was not. Moreover, a significant association was not observed between MCM3 and Ki-67, but the MCM3 LI was considerably higher. Western blot analyses revealed that the MCM3 protein expression levels were overexpressed in all PTCs. On the contrary, the levels of MCM3 were very low or absent in all normal thyroid tissues. Our results indicate that MCM3 may be a more reliable proliferation marker than Ki-67 in accessing the growth of tumor and evaluating tumor aggressiveness of PTC.
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Cyclin-dependent kinases (CDKs) mediate proliferation and neuronal development, while aberrant CDK activity is associated with cancer and neurodegeneration [1–5].
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A third mechanism permitting a ploidy increase is endomitosis: chromosomal DNA replication in the absence of karyokinesis and cytokinesis (57, 58). In yeast, overreplication can be induced by a number of perturbations, including decreased CDC16, CDC27, or G2 cyclin/p34Cdc28 activity or high levels of specific components of the DNA replication machinery (35, 59,60). In Saccharomyces cerevisiae, Cdc6p, a component of the pre-replication complex, is required to limit DNA replication to once per cell cycle (31, 61, 62).
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Cell cycle control of replication initiation in eukaryotes

Abstract

Science

Proc Natl Acad Sci USA

EMBO J

Mol Cell Biol

Curr Opin Genet Dev

EMBO J

J Cell Biol

EMBO J

Cell

Cell

Genes Dev

Curr Biol

Replication origins in eukaroytes

Curr Opin Genet Dev

The origin recognition complex in silencing, cell cycle progression and DNA replication

Mol Biol Cell

The origin recognition complex has essential functions in transcriptional silencing and chromosomal replication

Genes Dev

ORC and Cdc6p interact and determine the frequency of initiation of DNA replication in the genome

Cell

The multidomain structure of Orc1p reveals similary to regulators of DNA replication and transcriptional silencing

Cell

A Drosophila homolog of the yeast origin recognition complex

Science

Role for a Xenopus Orc2-related protein in controlling DNA replication

Nature

Interaction of cdc2 and cdc18 with a fission yeast orc2-like protein

Nature

Mouse and human homologues of the yeast origin of replication recognition complex subunit ORC2 and chromosomal localization of the cognate human gene ORC2L

Genomics

Interaction between the origin recognition complex and the replication licensing system in Xenopus

Cell

Overview of the regulation of S phase in Xenopus egg extracts

Biochimie

The DNA replication licensing system

Cancer Surveys

Stepwise assembly of initiation-complexes at budding yeast replication origins during the cell-cycle

J Cell Sci

P65(Cdc18) plays a major role controlling the initiation of DNA replication in fission yeast

Cell

Cdc18(+) regulates initiation of DNA replication in Schizosaccharomyces pombe

Proc Natl Acad Sci USA

An essential role for the cdc6 protein in forming the pre-replicative complexes of budding yeast

Nature

Interaction of Dbf4, the Cdc7 protein-kinase requlatory subunit, with yeast replication origins in vivo

Science

Hsk1(+), a Schizosaccharomyces pombe gene related to Saccharomyces cerevisiae Cdc7, is required for chromosomal replication

EMBO J

The role of MCM/P1 proteins in the licensing of DNA replication

Trends Biochem Sci

Purification of an Mcm-containing complex as a component of the DNA replication licensing system

Nature

Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor

Cell