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Nucleic Acids Res
2002 Jan 15;302:569-73. doi: 10.1093/nar/30.2.569.
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An oxidized nucleotide affects DNA replication through activation of protein kinases in Xenopus egg lysates.
Kai T
,
Matsunaga R
,
Eguchi M
,
Kamiya H
,
Kasai H
,
Suzuki M
,
Izuta S
.
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To elucidate the response to oxidative stress in eukaryotic cells, the effect of an oxidized nucleotide, 8-oxo-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP), generated from dGTP with an active oxygen, on DNA synthesis was studied using a cell-free DNA replication system derived from Xenopus egg lysates with a single-stranded DNA template. Amounts of newly synthesized DNA were reduced according to the increasing concentration of 8-oxo-dGTP. Pulse labeling analysis revealed that 8-oxo-dGTP could delay DNA synthesis by reducing the rate of chain elongation. This delay was recovered by addition of a protein kinase inhibitor, staurosporine or bisindolylmaleimide I. These results indicate that a staurosporine- or bisindolylmaleimide I-sensitive protein kinase, such as a protein kinase C family member, may contribute to the delay of DNA synthesis by 8-oxo-dGTP. UV-irradiated single-stranded DNA also caused a delay of DNA synthesis on the undamaged template in the lysates. However, this delay was not recovered by staurosporine or bisindolylmaleimide I. Therefore, the mechanism of delay of DNA synthesis by 8-oxo-dGTP may be different from that by UV lesions. This is the first report that demonstrates an effect of an oxidized nucleotide on DNA replication in eukaryotes.
Blasina,
Caffeine inhibits the checkpoint kinase ATM.
1999, Pubmed
Blasina,
Caffeine inhibits the checkpoint kinase ATM.
1999,
Pubmed
Blow,
Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs.
1986,
Pubmed
,
Xenbase
Cheng,
8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G----T and A----C substitutions.
1992,
Pubmed
Coleman,
The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA replication in cell-free extracts.
1996,
Pubmed
,
Xenbase
Einolf,
Steady-state and pre-steady-state kinetic analysis of 8-oxo-7,8-dihydroguanosine triphosphate incorporation and extension by replicative and repair DNA polymerases.
1998,
Pubmed
Elledge,
Cell cycle checkpoints: preventing an identity crisis.
1996,
Pubmed
Flattery-O'Brien,
Hydrogen peroxide causes RAD9-dependent cell cycle arrest in G2 in Saccharomyces cerevisiae whereas menadione causes G1 arrest independent of RAD9 function.
1998,
Pubmed
Hall-Jackson,
ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK.
1999,
Pubmed
Hartwell,
Checkpoints: controls that ensure the order of cell cycle events.
1989,
Pubmed
Kamath-Loeb,
Incorporation of the guanosine triphosphate analogs 8-oxo-dGTP and 8-NH2-dGTP by reverse transcriptases and mammalian DNA polymerases.
1997,
Pubmed
Kasai,
Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents.
1984,
Pubmed
Kaufmann,
Mechanisms of inhibition of DNA replication by ultraviolet light in normal human and xeroderma pigmentosum fibroblasts.
1981,
Pubmed
Kumagai,
14-3-3 proteins act as negative regulators of the mitotic inducer Cdc25 in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase
Lee,
Comparison of the efficacy of 7-hydroxystaurosporine (UCN-01) and other staurosporine analogs to abrogate cisplatin-induced cell cycle arrest in human breast cancer cell lines.
1999,
Pubmed
Liu,
Identification of the Xenopus laevis homolog of Saccharomyces cerevisiae DNA2 and its role in DNA replication.
2000,
Pubmed
,
Xenbase
Martinho,
Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses.
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
Michael,
Activation of the DNA replication checkpoint through RNA synthesis by primase.
2000,
Pubmed
,
Xenbase
Miller,
8-oxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279.
2000,
Pubmed
Morozova,
DNA damage-dependent inactivation of complementary strand synthesis in Xenopus laevis egg or HeLa cell lysates.
1998,
Pubmed
,
Xenbase
Pavlov,
DNA replication fidelity with 8-oxodeoxyguanosine triphosphate.
1994,
Pubmed
Sarkaria,
Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine.
1999,
Pubmed
Sekiguchi,
MutT-related error avoidance mechanism for DNA synthesis.
1996,
Pubmed
Tamaoki,
Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase.
1986,
Pubmed
Toullec,
The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.
1991,
Pubmed
Weinert,
DNA damage and checkpoint pathways: molecular anatomy and interactions with repair.
1998,
Pubmed
