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Literature DB >> 11018019

Unphosphorylatable mutants of Cdc6 disrupt its nuclear export but still support DNA replication once per cell cycle.

C Pelizon¹, M A Madine, P Romanowski, R A Laskey.

Abstract

Cdc6 is essential for eukaryotic DNA replication. We have mutated highly conserved CDK phosphorylation sites in Cdc6. Contrary to their reported phenotypes in human cells, unphosphorylatable DeltaCDK mutants fully support DNA replication in Xenopus eggs. WtCdc6 is actively exported from the nucleus, which could explain why nuclear permeabilization is required for reinitiation within one cell cycle. However, DeltaCDK mutants are retained in the nucleus, yet surprisingly they still support only one round of replication. As these highly conserved CDK sites are unnecessary for replication once per cell cycle, an alternative checkpoint role for monitoring completion of the S phase is suggested.

Entities: Chemical Gene Species

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Year: 2000 PMID： 11018019 PMCID： PMC316983 DOI： 10.1101/gad.176300

Source DB: PubMed Journal: Genes Dev ISSN： 0890-9369 Impact factor: 11.361

30 in total

1. Mechanisms restricting DNA replication to once per cell cycle: MCMS, pre-replicative complexes and kinases.

Authors: P Romanowski; M A Madine
Journal: Trends Cell Biol Date: 1996-05 Impact factor: 20.808

2. The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA replication in cell-free extracts.

Authors: T R Coleman; P B Carpenter; W G Dunphy
Journal: Cell Date: 1996-10-04 Impact factor: 41.582

3. Interaction of the S phase regulator cdc18 with cyclin-dependent kinase in fission yeast.

Authors: G W Brown; P V Jallepalli; B J Huneycutt; T J Kelly
Journal: Proc Natl Acad Sci U S A Date: 1997-06-10 Impact factor: 11.205

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Authors: J J Blow; R A Laskey
Journal: Nature Date: 1988-04-07 Impact factor: 49.962

5. The Xenopus origin recognition complex is essential for DNA replication and MCM binding to chromatin.

Authors: P Romanowski; M A Madine; A Rowles; J J Blow; R A Laskey
Journal: Curr Biol Date: 1996-11-01 Impact factor: 10.834

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

Authors: C Dahmann; J F Diffley; K A Nasmyth
Journal: Curr Biol Date: 1995-11-01 Impact factor: 10.834

7. The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.

Authors: E Schwob; T Böhm; M D Mendenhall; K Nasmyth
Journal: Cell Date: 1994-10-21 Impact factor: 41.582

8. Chromatin-bound Cdc6 persists in S and G2 phases in human cells, while soluble Cdc6 is destroyed in a cyclin A-cdk2 dependent process.

Authors: D Coverley; C Pelizon; S Trewick; R A Laskey
Journal: J Cell Sci Date: 2000-06 Impact factor: 5.285

9. Dual functions of CDC6: a yeast protein required for DNA replication also inhibits nuclear division.

Authors: A Bueno; P Russell
Journal: EMBO J Date: 1992-06 Impact factor: 11.598

10. Cdc6 is an unstable protein whose de novo synthesis in G1 is important for the onset of S phase and for preventing a 'reductional' anaphase in the budding yeast Saccharomyces cerevisiae.

Authors: S Piatti; C Lengauer; K Nasmyth
Journal: EMBO J Date: 1995-08-01 Impact factor: 11.598

26 in total

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Authors: Jeanette Gowen Cook; Chi-Hyun Park; Thomas W Burke; Gustavo Leone; James DeGregori; Amber Engel; Joseph R Nevins
Journal: Proc Natl Acad Sci U S A Date: 2002-01-22 Impact factor: 11.205

2. Cell cycle-dependent regulation of the association between origin recognition proteins and somatic cell chromatin.

Authors: Wei-Hsin Sun; Thomas R Coleman; Melvin L DePamphilis
Journal: EMBO J Date: 2002-03-15 Impact factor: 11.598

3. Xenopus Cdc6 performs separate functions in initiating DNA replication.

Authors: Natalya S Frolova; Nancy Schek; Nadia Tikhmyanova; Thomas R Coleman
Journal: Mol Biol Cell Date: 2002-04 Impact factor: 4.138

4. Stability, chromatin association and functional activity of mammalian pre-replication complex proteins during the cell cycle.

Authors: Y Okuno; A J McNairn; N den Elzen; J Pines; D M Gilbert
Journal: EMBO J Date: 2001-08-01 Impact factor: 11.598

5. Retinoblastoma tumor suppressor protein signals through inhibition of cyclin-dependent kinase 2 activity to disrupt PCNA function in S phase.

Authors: Z Sever-Chroneos; S P Angus; A F Fribourg; H Wan; I Todorov; K E Knudsen; E S Knudsen
Journal: Mol Cell Biol Date: 2001-06 Impact factor: 4.272

6. Cdc6 chromatin affinity is unaffected by serine-54 phosphorylation, S-phase progression, and overexpression of cyclin A.

Authors: Mark G Alexandrow; Joyce L Hamlin
Journal: Mol Cell Biol Date: 2004-02 Impact factor: 4.272

7. CDK phosphorylation of a novel NLS-NES module distributed between two subunits of the Mcm2-7 complex prevents chromosomal rereplication.

Authors: Muluye E Liku; Van Q Nguyen; Audrey W Rosales; Kaoru Irie; Joachim J Li
Journal: Mol Biol Cell Date: 2005-08-10 Impact factor: 4.138