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Genes Dev
2000 Nov 01;1421:2745-56. doi: 10.1101/gad.842500.
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Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts.
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The checkpoint kinase Xchk1 becomes phosphorylated in Xenopus egg extracts in response to DNA replication blocks or UV-damaged DNA. Xchk1 is also required for the cell cycle delay that is induced by unreplicated or UV-damaged DNA. In this report, we have removed the Xenopus homolog of ATR (Xatr) from egg extracts by immunodepletion. In Xatr-depleted extracts, the checkpoint-associated phosphorylation of Xchk1 is abolished, and the cell cycle delay induced by replication blocks is strongly compromised. Xatr from egg extracts phosphorylated recombinant Xchk1 in vitro, but not a mutant form of Xchk1 (Xchk1-4AQ) containing nonphosphorylatable residues in its four conserved SQ/TQ motifs. Recombinant human ATR, but not a kinase-inactive mutant, phosphorylated the same sites in Xchk1. Furthermore, the Xchk1-4AQ mutant was found to be defective in mediating a checkpoint response in egg extracts. These findings suggest that Xchk1 is a functionally important target of Xatr during a checkpoint response to unreplicated or UV-damaged DNA.
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11069891
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Adachi,
Identification of nuclear pre-replication centers poised for DNA synthesis in Xenopus egg extracts: immunolocalization study of replication protein A.
1992, Pubmed,
Xenbase
Adachi,
Identification of nuclear pre-replication centers poised for DNA synthesis in Xenopus egg extracts: immunolocalization study of replication protein A.
1992,
Pubmed
,
Xenbase
Banin,
Enhanced phosphorylation of p53 by ATM in response to DNA damage.
1998,
Pubmed
Bentley,
The Schizosaccharomyces pombe rad3 checkpoint gene.
1996,
Pubmed
Blasina,
A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase.
1999,
Pubmed
Blasina,
Caffeine inhibits the checkpoint kinase ATM.
1999,
Pubmed
Brondello,
Basis for the checkpoint signal specificity that regulates Chk1 and Cds1 protein kinases.
1999,
Pubmed
Brown,
A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage.
1999,
Pubmed
Brown,
ATR disruption leads to chromosomal fragmentation and early embryonic lethality.
2000,
Pubmed
Canman,
Activation of the ATM kinase by ionizing radiation and phosphorylation of p53.
1998,
Pubmed
Chan,
14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage.
1999,
Pubmed
Chaturvedi,
Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway.
1999,
Pubmed
Chehab,
Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53.
2000,
Pubmed
Cimprich,
cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein.
1996,
Pubmed
Cliby,
Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints.
1998,
Pubmed
Cortez,
Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks.
1999,
Pubmed
de Klein,
Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice.
2000,
Pubmed
Dohmen,
An essential yeast gene encoding a homolog of ubiquitin-activating enzyme.
1995,
Pubmed
Elledge,
Cell cycle checkpoints: preventing an identity crisis.
1996,
Pubmed
Fogarty,
The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity.
1997,
Pubmed
Frangioni,
Solubilization and purification of enzymatically active glutathione S-transferase (pGEX) fusion proteins.
1993,
Pubmed
Gatei,
ATM-dependent phosphorylation of nibrin in response to radiation exposure.
2000,
Pubmed
Gaudette,
Replication forks are underrepresented in chromosomal DNA of Xenopus laevis embryos.
1986,
Pubmed
,
Xenbase
Guo,
Response of Xenopus Cds1 in cell-free extracts to DNA templates with double-stranded ends.
2000,
Pubmed
,
Xenbase
Hall-Jackson,
ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK.
1999,
Pubmed
Hirao,
DNA damage-induced activation of p53 by the checkpoint kinase Chk2.
2000,
Pubmed
Keegan,
The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes.
1996,
Pubmed
Kim,
Substrate specificities and identification of putative substrates of ATM kinase family members.
1999,
Pubmed
Kinoshita,
The identification of two novel ligands of the FGF receptor by a yeast screening method and their activity in Xenopus development.
1995,
Pubmed
,
Xenbase
Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase
Kumagai,
Binding of 14-3-3 proteins and nuclear export control the intracellular localization of the mitotic inducer Cdc25.
1999,
Pubmed
,
Xenbase
Lavin,
The genetic defect in ataxia-telangiectasia.
1997,
Pubmed
Lim,
ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.
2000,
Pubmed
Lindahl,
Quality control by DNA repair.
1999,
Pubmed
Lindsay,
S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe.
1998,
Pubmed
Liu,
Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint.
2000,
Pubmed
Lopez-Girona,
Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein.
1999,
Pubmed
Mahbubani,
Cell cycle regulation of the replication licensing system: involvement of a Cdk-dependent inhibitor.
1997,
Pubmed
,
Xenbase
Matsuoka,
Linkage of ATM to cell cycle regulation by the Chk2 protein kinase.
1998,
Pubmed
Méchali,
DNA synthesis in a cell-free system from Xenopus eggs: priming and elongation on single-stranded DNA in vitro.
1982,
Pubmed
,
Xenbase
Mitchell,
Vectors for the inducible overexpression of glutathione S-transferase fusion proteins in yeast.
1993,
Pubmed
Mueller,
Cell cycle regulation of a Xenopus Wee1-like kinase.
1995,
Pubmed
,
Xenbase
Murakami,
A kinase from fission yeast responsible for blocking mitosis in S phase.
1995,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
O'Connell,
The G2-phase DNA-damage checkpoint.
2000,
Pubmed
Robertson,
Isolation and characterization of Xenopus ATM (X-ATM): expression, localization, and complex formation during oogenesis and early development.
1999,
Pubmed
,
Xenbase
Sanchez,
Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways.
1996,
Pubmed
Sanchez,
Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25.
1997,
Pubmed
Sarkaria,
Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine.
1999,
Pubmed
Shieh,
The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites.
2000,
Pubmed
Sibon,
DNA-replication checkpoint control at the Drosophila midblastula transition.
1997,
Pubmed
Smith,
The DNA-dependent protein kinase.
1999,
Pubmed
Smith,
Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM.
1999,
Pubmed
Suzuki,
Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation.
1999,
Pubmed
Takai,
Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice.
2000,
Pubmed
Tibbetts,
A role for ATR in the DNA damage-induced phosphorylation of p53.
1999,
Pubmed
Tominaga,
Role of human Cds1 (Chk2) kinase in DNA damage checkpoint and its regulation by p53.
1999,
Pubmed
Walworth,
rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint.
1996,
Pubmed
Wright,
Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control.
1998,
Pubmed
Yang,
Maintenance of G2 arrest in the Xenopus oocyte: a role for 14-3-3-mediated inhibition of Cdc25 nuclear import.
1999,
Pubmed
,
Xenbase
Zeng,
DNA damage and replication checkpoints in fission yeast require nuclear exclusion of the Cdc25 phosphatase via 14-3-3 binding.
1999,
Pubmed
