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Mol Biol Cell
2002 May 01;135:1536-49. doi: 10.1091/mbc.02-02-0010.
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Targeted destruction of DNA replication protein Cdc6 by cell death pathways in mammals and yeast.
Blanchard F
,
Rusiniak ME
,
Sharma K
,
Sun X
,
Todorov I
,
Castellano MM
,
Gutierrez C
,
Baumann H
,
Burhans WC
.
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The highly conserved Cdc6 protein is required for initiation of eukaryotic DNA replication and, in yeast and Xenopus, for the coupling of DNA replication to mitosis. Herein, we show that human Cdc6 is rapidly destroyed by a p53-independent, proteasome-, and ubiquitin-dependent pathway during early stages of programmed cell death induced by the DNA-damaging drug adozelesin, or by a separate caspase-dependent pathway in cells undergoing apoptosis through an extrinsic pathway induced by tumor necrosis factor-alpha and cycloheximide. The proteasome-dependent pathway induced by adozelesin is conserved in the budding yeast Saccharomyces cerevisiae. The destruction of Cdc6 may be a primordial programmed death response that uncouples DNA replication from the cell division cycle, which is reinforced in metazoans by the evolution of caspases and p53.
Agami,
Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage.
2000, Pubmed
Agami,
Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage.
2000,
Pubmed
Anderson,
Cancer: the evolved consequence of a destabilized genome.
2001,
Pubmed
Bhuyan,
Adozelesin, a potent new alkylating agent: cell-killing kinetics and cell-cycle effects.
1992,
Pubmed
Bhuyan,
Lethality, DNA alkylation, and cell cycle effects of adozelesin (U-73975) on rodent and human cells.
1992,
Pubmed
Brewer,
The localization of replication origins on ARS plasmids in S. cerevisiae.
1987,
Pubmed
Bueno,
Dual functions of CDC6: a yeast protein required for DNA replication also inhibits nuclear division.
1992,
Pubmed
Calzada,
The stability of the Cdc6 protein is regulated by cyclin-dependent kinase/cyclin B complexes in Saccharomyces cerevisiae.
2000,
Pubmed
Carty,
UV light-induced DNA synthesis arrest in HeLa cells is associated with changes in phosphorylation of human single-stranded DNA-binding protein.
1994,
Pubmed
Castellano,
Expression and stability of Arabidopsis CDC6 are associated with endoreplication.
2001,
Pubmed
Chai,
Involvement of p21(Waf1/Cip1) and its cleavage by DEVD-caspase during apoptosis of colorectal cancer cells induced by butyrate.
2000,
Pubmed
Cobuzzi,
Inhibition of initiation of simian virus 40 DNA replication in infected BSC-1 cells by the DNA alkylating drug adozelesin.
1996,
Pubmed
Dallaporta,
Proteasome activation as a critical event of thymocyte apoptosis.
2000,
Pubmed
Desdouets,
Evidence for a Cdc6p-independent mitotic resetting event involving DNA polymerase alpha.
1998,
Pubmed
Detweiler,
Cdc6p establishes and maintains a state of replication competence during G1 phase.
1997,
Pubmed
Diffley,
DNA replication: building the perfect switch.
2001,
Pubmed
Diffley,
Two steps in the assembly of complexes at yeast replication origins in vivo.
1994,
Pubmed
,
Xenbase
Dijkwel,
Mapping of replication initiation sites in mammalian genomes by two-dimensional gel analysis: stabilization and enrichment of replication intermediates by isolation on the nuclear matrix.
1991,
Pubmed
Drury,
The cyclin-dependent kinase Cdc28p regulates distinct modes of Cdc6p proteolysis during the budding yeast cell cycle.
2000,
Pubmed
Drury,
The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast.
1997,
Pubmed
Dutta,
Initiation of DNA replication in eukaryotic cells.
1997,
Pubmed
Elsasser,
Interaction between yeast Cdc6 protein and B-type cyclin/Cdc28 kinases.
1996,
Pubmed
Falck,
The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis.
2001,
Pubmed
Folkman,
Cancer: looking outside the genome.
2000,
Pubmed
Fujita,
Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation.
1999,
Pubmed
Furstenthal,
Cyclin E uses Cdc6 as a chromatin-associated receptor required for DNA replication.
2001,
Pubmed
,
Xenbase
Guo,
Cell proliferation and apoptosis.
1999,
Pubmed
Hateboer,
Cell cycle-regulated expression of mammalian CDC6 is dependent on E2F.
1998,
Pubmed
Hekmat-Nejad,
Xenopus ATR is a replication-dependent chromatin-binding protein required for the DNA replication checkpoint.
,
Pubmed
,
Xenbase
Hengartner,
The biochemistry of apoptosis.
2000,
Pubmed
Kellokumpu-Lehtinen,
Leukemia-inhibitory factor stimulates breast, kidney and prostate cancer cell proliferation by paracrine and autocrine pathways.
1996,
Pubmed
Kelly,
The fission yeast cdc18+ gene product couples S phase to START and mitosis.
1993,
Pubmed
Kelly,
Coupling DNA replication to the cell cycle.
1993,
Pubmed
Kurokawa,
Alteration of caspase-3 (CPP32/Yama/apopain) in wild-type MCF-7, breast cancer cells.
1999,
Pubmed
Levkau,
Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade.
1998,
Pubmed
Lipinski,
The retinoblastoma gene family in differentiation and development.
1999,
Pubmed
Liu,
Adozelesin triggers DNA damage response pathways and arrests SV40 DNA replication through replication protein A inactivation.
2000,
Pubmed
Madine,
The roles of the MCM, ORC, and Cdc6 proteins in determining the replication competence of chromatin in quiescent cells.
2000,
Pubmed
,
Xenbase
Mailand,
Rapid destruction of human Cdc25A in response to DNA damage.
2000,
Pubmed
Michael,
Activation of the DNA replication checkpoint through RNA synthesis by primase.
2000,
Pubmed
,
Xenbase
Méndez,
Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.
2000,
Pubmed
,
Xenbase
Perkins,
Separate SCF(CDC4) recognition elements target Cdc6 for proteolysis in S phase and mitosis.
2001,
Pubmed
Petersen,
Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1.
2000,
Pubmed
Piatti,
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.
1995,
Pubmed
Shirahige,
Regulation of DNA-replication origins during cell-cycle progression.
1998,
Pubmed
Stewart,
Leukaemia inhibitory factor and the regulation of pre-implantation development of the mammalian embryo.
1994,
Pubmed
Stoeber,
DNA replication licensing and human cell proliferation.
2001,
Pubmed
Tavormina,
Differential requirements for DNA replication in the activation of mitotic checkpoints in Saccharomyces cerevisiae.
1997,
Pubmed
Thor,
Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers.
1992,
Pubmed
Toyn,
Segregation of unreplicated chromosomes in Saccharomyces cerevisiae reveals a novel G1/M-phase checkpoint.
1995,
Pubmed
Treuner,
Hyperphosphorylation of replication protein A middle subunit (RPA32) in apoptosis.
1999,
Pubmed
Vigo,
CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase.
1999,
Pubmed
Weinberger,
Induction by adozelesin and hydroxyurea of origin recognition complex-dependent DNA damage and DNA replication checkpoints in Saccharomyces cerevisiae.
1999,
Pubmed
Weinreich,
Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle.
2001,
Pubmed
Williams,
Improved cervical smear assessment using antibodies against proteins that regulate DNA replication.
1998,
Pubmed
Yan,
Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.
1998,
Pubmed
Yin,
Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles.
1992,
Pubmed