Scheduled Conversion of Replication Complex Architecture at Replication Origins of Saccharomyces cerevisiae during the Cell Cycle

Tadokoro, Ryusuke; Fujita, Masako; Miura, Hitoshi; Shirahige, Katsuhiko; Yoshikawa, Hiroshi; Tsurimoto, Toshiki; Obuse, Chikashi

doi:10.1074/jbc.m200322200

Cited by 6 publications

(2 citation statements)

References 31 publications

(58 reference statements)

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“…(18,19) In yeast, MCM2-7 dissociate from origins either upon replication initiation (20,21) or upon passive replication from a neighboring origin. (22,23) Biochemical and immunofluorescence studies in metazoan cells also suggest that MCMs are progressively excluded from replicated chromatin during S phase. (24)(25)(26)(27)(28)(29) The reloading of MCMs is prevented until cells pass through mitosis by CDKs and by geminin.…”

Section: Introductionmentioning

confidence: 99%

Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem

2003

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Eukaryotic DNA replication initiates at multiple origins. In early fly and frog embryos, chromosomal replication is very rapid and initiates without sequence specificity. Despite this apparent randomness, the spacing of these numerous initiation sites must be sufficiently regular for the genome to be completely replicated on time. Studies in various eukaryotes have revealed that there is a strict temporal separation of origin "licensing" prior to S phase and origin activation during S phase. This may suggest that replicon size must be already established at the licensing stage. However, recent experiments suggest that a large excess of potential origins are assembled along chromatin during licensing. Thus, a regular replicon size may result from the selection of origins during S phase. We review single molecule analyses of origin activation and other experiments addressing this issue and their general significance for eukaryotic DNA replication.

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Section: Introductionmentioning

confidence: 99%

Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem

2003

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“…For example, minichromosome maintenance (MCM) proteins are loaded onto origins in the presence of ORC and CDC6, which establishes the pre-replicative complex (pre-RC) necessary for subsequent protein assembly (9 -13). After origin firing, the pre-RC changes to a post-replicative form by the dissociation of MCM from the complex (12,14,15). These associations provide an important mechanism that 1) ensures that replication origins fire at precise times and 2) prevents re-initiation.…”

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confidence: 99%

The ORC1 Cycle in Human Cells

Tatsumi

Ohta

Kimura

et al. 2003

Journal of Biological Chemistry

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102

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Components of ORC (the origin recognition complex) are highly conserved among eukaryotes and are thought to play an essential role in the initiation of DNA replication. The level of the largest subunit of human ORC (ORC1) during the cell cycle was studied in several human cell lines with a specific antibody. In all cell lines, ORC1 levels oscillate: ORC1 starts to accumulate in mid-G 1 phase, reaches a peak at the G 1 /S boundary, and decreases to a basal level in S phase. In contrast, the levels of other ORC subunits (ORCs 2-5) remain constant throughout the cell cycle. The oscillation of ORC1, or the ORC1 cycle, also occurs in cells expressing ORC1 ectopically from a constitutive promoter. Furthermore, the 26 S proteasome inhibitor MG132 blocks the decrease in ORC1, suggesting that the ORC1 cycle is mainly due to 26 S proteasome-dependent degradation. Arrest of the cell cycle in early S phase by hydroxyurea, aphidicolin, or thymidine treatment is associated with basal levels of ORC1, indicating that ORC1 proteolysis starts in early S phase and is independent of S phase progression. These observations indicate that the ORC1 cycle in human cells is highly linked with cell cycle progression, allowing the initiation of replication to be coordinated with the cell cycle and preventing origins from refiring.The replication of chromosomal DNA in eukaryotes is limited to once per cell division cycle. This control appears to be achieved mainly by the regulation of replication origins so that they fire only once per cell cycle. The origin recognition complex (ORC), 1 identified in budding yeast as a protein complex that binds origins, consists of six gene products (1-5). In addition to ORC, several factors highly conserved among eukaryotes are involved in initiation (6 -8). The sequential assembly of these factors on origin-ORC complexes precedes initiation, as has been shown in yeast and Xenopus systems. For example, minichromosome maintenance (MCM) proteins are loaded onto origins in the presence of ORC and CDC6, which establishes the pre-replicative complex (pre-RC) necessary for subsequent protein assembly (9 -13). After origin firing, the pre-RC changes to a post-replicative form by the dissociation of MCM from the complex (12, 14, 15). These associations provide an important mechanism that 1) ensures that replication origins fire at precise times and 2) prevents re-initiation. Budding yeast ORC is a static complex that is maintained at a constant level and remains bound to origins throughout the cell cycle (4, 5). Thus, MCM loading in yeast is mainly regulated by other factors such as cell cycle-regulated Cdc6 or CDK kinase activities (7,8,16). It is also known that the phosphorylation status of ORC subunits correlates with the timing of pre-RC formation, suggesting a role for ORC phosphorylation in MCM loading (16). Similar phosphorylation of ORC subunits was found in a Xenopus egg extract system, suggesting a conserved mechanism for the regulation of ORC functions (17, 18). Recent studies have elucidated possible...

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Current Awareness on Yeast

2002

Yeast

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In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (3 weeks journals ‐ search completed 26th. June 2002)

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Scheduled Conversion of Replication Complex Architecture at Replication Origins of Saccharomyces cerevisiae during the Cell Cycle

Cited by 6 publications

References 31 publications

Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem

Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem

The ORC1 Cycle in Human Cells

Current Awareness on Yeast

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