scholarly journals Notch and Minichromosome Maintenance (MCM) Proteins: Integration of Two Ancestral Pathways in Cell Cycle Control

Cell Cycle ◽  
2006 ◽  
Vol 5 (23) ◽  
pp. 2704-2709 ◽  
Author(s):  
Michela Noseda ◽  
Aly Karsan
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control ◽  
Minichromosome Maintenance ◽  
Mcm Proteins

The role of MCM proteins in the cell cycle control of genome duplication

BioEssays ◽  
1996 ◽  
Vol 18 (3) ◽  
pp. 183-190 ◽  
Author(s):  
Stephen E. Kearsey ◽  
Domenico Maiorano ◽  
Eddie C. Holmes ◽  
Ivan T. Todorov
Keyword(s):  
Cell Cycle ◽  
Genome Duplication ◽  
Cell Cycle Control ◽  
Mcm Proteins

scholarly journals Drosophila Minichromosome Maintenance 6 Is Required for Chorion Gene Amplification and Genomic Replication

2002 ◽  
Vol 13 (2) ◽  
pp. 607-620 ◽  
Author(s):  
Gina Schwed ◽  
Noah May ◽  
Yana Pechersky ◽  
Brian R. Calvi
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Genetic Dissection ◽  
Minichromosome Maintenance ◽  
Multiple Origins ◽  
Origin Licensing ◽  
Mcm Complex ◽  
Mcm Proteins ◽  
Prereplicative Complex ◽  
Cycle Regulation

Duplication of the eukaryotic genome initiates from multiple origins of DNA replication whose activity is coordinated with the cell cycle. We have been studying the origins of DNA replication that control amplification of eggshell (chorion) genes duringDrosophila oogenesis. Mutation of genes required for amplification results in a thin eggshell phenotype, allowing a genetic dissection of origin regulation. Herein, we show that one mutation corresponds to a subunit of the minichromosome maintenance (MCM) complex of proteins, MCM6. The binding of the MCM complex to origins in G1 as part of a prereplicative complex is critical for the cell cycle regulation of origin licensing. We find that MCM6 associates with other MCM subunits during amplification. These results suggest that chorion origins are bound by an amplification complex that contains MCM proteins and therefore resembles the prereplicative complex. Lethal alleles of MCM6 reveal it is essential for mitotic cycles and endocycles, and suggest that its function is mediated by ATP. We discuss the implications of these findings for the role of MCMs in the coordination of DNA replication during the cell cycle.

scholarly journals Chromosome Association of Minichromosome Maintenance Proteins in Drosophila Mitotic Cycles

1997 ◽  
Vol 139 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Tin Tin Su ◽  
Patrick H. O'Farrell
Keyword(s):  
Cell Cycle ◽  
Cyclin E ◽  
Embryonic Cell ◽  
Cyclin B ◽  
Chromatin Interaction ◽  
G1 Phase ◽  
Minichromosome Maintenance ◽  
Cell Cycles ◽  
Mcm Proteins ◽  
Replication Factors

Minichromosome maintenance (MCM) proteins are essential DNA replication factors conserved among eukaryotes. MCMs cycle between chromatin bound and dissociated states during each cell cycle. Their absence on chromatin is thought to contribute to the inability of a G2 nucleus to replicate DNA. Passage through mitosis restores the ability of MCMs to bind chromatin and the ability to replicate DNA. In Drosophila early embryonic cell cycles, which lack a G1 phase, MCMs reassociate with condensed chromosomes toward the end of mitosis. To explore the coupling between mitosis and MCM–chromatin interaction, we tested whether this reassociation requires mitotic degradation of cyclins. Arrest of mitosis by induced expression of nondegradable forms of cyclins A and/or B showed that reassociation of MCMs to chromatin requires cyclin A destruction but not cyclin B destruction. In contrast to the earlier mitoses, mitosis 16 (M16) is followed by G1, and MCMs do not reassociate with chromatin at the end of M16. dacapo mutant embryos lack an inhibitor of cyclin E, do not enter G1 quiescence after M16, and show mitotic reassociation of MCM proteins. We propose that cyclin E, inhibited by Dacapo in M16, promotes chromosome binding of MCMs. We suggest that cyclins have both positive and negative roles in controlling MCM–chromatin association.

scholarly journals Association of Fission Yeast Orp1 and Mcm6 Proteins with Chromosomal Replication Origins

1999 ◽  
Vol 19 (10) ◽  
pp. 7228-7236 ◽  
Author(s):  
Yuya Ogawa ◽  
Tatsuro Takahashi ◽  
Hisao Masukata
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Chromatin Immunoprecipitation ◽  
Origin Recognition Complex ◽  
Replication Origins ◽  
Minichromosome Maintenance ◽  
Chromatin Immunoprecipitation Assay ◽  
Chromosomal Replication ◽  
Initiation Of Replication ◽  
Mcm Proteins

ABSTRACT We have previously shown that replication of fission yeast chromosomes is initiated in distinct regions. Analyses of autonomous replicating sequences have suggested that regions required for replication are very different from those in budding yeast. Here, we present evidence that fission yeast replication origins are specifically associated with proteins that participate in initiation of replication. Most Orp1p, a putative subunit of the fission yeast origin recognition complex (ORC), was found to be associated with chromatin-enriched insoluble components throughout the cell cycle. In contrast, the minichromosome maintenance (Mcm) proteins, SpMcm2p and SpMcm6p, encoded by thenda1 +/cdc19+ andmis5+ genes, respectively, were associated with chromatin DNA only during the G1 and S phases. Immunostaining of spread nuclei showed SpMcm6p to be localized at discrete foci on chromatin during the G1 and S phases. A chromatin immunoprecipitation assay demonstrated that Orp1p was preferentially localized at the ars2004 andars3002 origins of the chromosome throughout the cell cycle, while SpMcm6p was associated with these origins only in the G1 and S phases. Both Orp1p and SpMcm6p were associated with a 1-kb region that contains elements required for autonomous replication of ars2004. The results suggest that the fission yeast ORC specifically interacts with chromosomal replication origins and that Mcm proteins are loaded onto the origins to play a role in initiation of replication.

scholarly journals Chromatin Association of Human Origin Recognition Complex, Cdc6, and Minichromosome Maintenance Proteins during the Cell Cycle: Assembly of Prereplication Complexes in Late Mitosis

2000 ◽  
Vol 20 (22) ◽  
pp. 8602-8612 ◽  
Author(s):  
Juan Méndez ◽  
Bruce Stillman
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Origin Recognition Complex ◽  
Proteasome Inhibitors ◽  
Minichromosome Maintenance ◽  
Mitotic Kinase ◽  
Late Mitosis ◽  
Mcm Proteins ◽  
Origin Recognition

ABSTRACT Evidence obtained from studies with yeast and Xenopusindicate that the initiation of DNA replication is a multistep process. The origin recognition complex (ORC), Cdc6p, and minichromosome maintenance (MCM) proteins are required for establishing prereplication complexes, upon which initiation is triggered by the activation of cyclin-dependent kinases and the Dbf4p-dependent kinase Cdc7p. The identification of human homologues of these replication proteins allows investigation of S-phase regulation in mammalian cells. Using centrifugal elutriation of several human cell lines, we demonstrate that whereas human Orc2 (hOrc2p) and hMcm proteins are present throughout the cell cycle, hCdc6p levels vary, being very low in early G1 and accumulating until cells enter mitosis. hCdc6p can be polyubiquitinated in vivo, and it is stabilized by proteasome inhibitors. Similar to the case for hOrc2p, a significant fraction of hCdc6p is present on chromatin throughout the cell cycle, whereas hMcm proteins alternate between soluble and chromatin-bound forms. Loading of hMcm proteins onto chromatin occurs in late mitosis concomitant with the destruction of cyclin B, indicating that the mitotic kinase activity inhibits prereplication complex formation in human cells.

scholarly journals Nascent Transcription of MCM2-7 Is Important for Nuclear Localization of the Minichromosome Maintenance Complex in G1

2007 ◽  
Vol 18 (4) ◽  
pp. 1447-1456 ◽  
Author(s):  
Katherine A. Braun ◽  
Linda L. Breeden
Keyword(s):  
Cell Cycle ◽  
Nuclear Localization ◽  
Nuclear Import ◽  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Minichromosome Maintenance ◽  
Mcm Complex ◽  
Mcm Proteins ◽  
Constitutive Production ◽  
New Protein

The minichromosome maintenance genes (MCM2-7) are transcribed at M/G1 just as the Mcm complex is imported into the nucleus to be assembled into prereplication complexes, during a period of low cyclin-dependent kinase (CDK) activity. The CDKs trigger DNA replication and prevent rereplication in part by exporting Mcm2-7 from the nucleus during S phase. We have found that repression of MCM2-7 transcription in a single cell cycle interferes with the nuclear import of Mcms in the subsequent M/G1 phase. This suggests that nascent Mcm proteins are preferentially imported into the nucleus. Consistent with this, we find that loss of CDK activity in G2/M is not sufficient for nuclear import, there is also a requirement for new protein synthesis. This requirement is not met by constitutive production of Cdc6 and does not involve synthesis of new transport machinery. The Mcm proteins generated in the previous cell cycle, which are unable to reaccumulate in the nucleus, are predominantly turned over by ubiquitin-mediated proteolysis in late mitosis/early G1. Therefore, the nuclear localization of Mcm2-7 is dependent on nascent transcription and translation of Mcm2-7 and the elimination of CDK activity which occurs simultaneously as cells enter G1.

scholarly journals The Croonian Lecture 2001 Hunting the antisocial cancer cell: MCM proteins and their exploitation

2005 ◽  
Vol 360 (1458) ◽  
pp. 1119-1132 ◽  
Author(s):  
Ronald Laskey
Keyword(s):  
Cell Cycle ◽  
Screening Tests ◽  
Eukaryotic Cells ◽  
Replication Forks ◽  
Minichromosome Maintenance ◽  
A Cell ◽  
The Common ◽  
Initiation Of Dna Replication ◽  
Mcm Proteins ◽  
Eukaryotic Genomes

Replicating large eukaryotic genomes presents the challenge of distinguishing replicated regions of DNA from unreplicated DNA. A heterohexamer of minichromosome maintenance (MCM) proteins is essential for the initiation of DNA replication. MCM proteins are loaded on to unreplicated DNA before replication begins and displaced progressively during replication. Thus, bound MCM proteins license DNA for one, and only one, round of replication and this licence is reissued each time a cell divides. MCM proteins are also the best candidates for the replicative helicases that unwind DNA during replication, but interesting questions arise about how they can perform this role, particularly as they are present on only unreplicated DNA, rather than clustered at replication forks. Although MCM proteins are bound and released cyclically from DNA during the cell cycle, higher eukaryotic cells retain them in the nucleus throughout the cell cycle. In contrast, MCMs are broken down when cells exit the cycle by quiescence or differentiation. We have exploited these observations to develop screening tests for the common carcinomas, starting with an attempt to improve the sensitivity of the smear test for cervical cancer. MCM proteins emerge as exceptionally promising markers for cancer screening and early diagnosis.

scholarly journals Chromosome Association of Minichromosome Maintenance Proteins in Drosophila Endoreplication Cycles

1998 ◽  
Vol 140 (3) ◽  
pp. 451-460 ◽  
Author(s):  
Tin Tin Su ◽  
Patrick H. O'Farrell
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Mitotic Cell ◽  
Chromosome Association ◽  
Minichromosome Maintenance ◽  
Chromosome Duplication ◽  
Chromosome Associations ◽  
Mcm Proteins ◽  
Polytene Nuclei ◽  
Replication Factors

Minichromosome maintenance (MCM) proteins are essential eukaryotic DNA replication factors. The binding of MCMs to chromatin oscillates in conjunction with progress through the mitotic cell cycle. This oscillation is thought to play an important role in coupling DNA replication to mitosis and limiting chromosome duplication to once per cell cycle. The coupling of DNA replication to mitosis is absent in Drosophila endoreplication cycles (endocycles), during which discrete rounds of chromosome duplication occur without intervening mitoses. We examined the behavior of MCM proteins in endoreplicating larval salivary glands, to determine whether oscillation of MCM–chromosome localization occurs in conjunction with passage through an endocycle S phase. We found that MCMs in polytene nuclei exist in two states: associated with or dissociated from chromosomes. We demonstrate that cyclin E can drive chromosome association of DmMCM2 and that DNA synthesis erases this association. We conclude that mitosis is not required for oscillations in chromosome binding of MCMs and propose that cycles of MCM–chromosome association normally occur in endocycles. These results are discussed in a model in which the cycle of MCM–chromosome associations is uncoupled from mitosis because of the distinctive program of cyclin expression in endocycles.

Tolerance to mucosally encountered antigen is linked to cell cycle control

2001 ◽  
Vol 120 (5) ◽  
pp. A322-A322
Author(s):  
M STALLS ◽  
J SUN ◽  
K THOMPSON ◽  
N VANHOUTEN
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control

983: Bladder Cancer Predisposition: A Pathway-Based Approach to DNA Repair and Cell Cycle Control Genes

2006 ◽  
Vol 175 (4S) ◽  
pp. 317-317
Author(s):  
Xifeng Wu ◽  
Jian Gu ◽  
H. Barton Grossman ◽  
Christopher I. Amos ◽  
Carol Etzel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Dna Repair ◽  
Cell Cycle Control ◽  
Cancer Predisposition
Sign in / Sign up

Export Citation Format

Share Document