Hydroxyurea: Inhibitory Effect on DNA Metabolism

Young, Charles W.; Hodas, Sadie

doi:10.1126/science.146.3648.1172

Cited by 398 publications

(106 citation statements)

References 7 publications

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“…Hydroxyurea inhibits ribonucleotide reductase, a key enzyme for the synthesis of deoxyribonucleotides. Hydroxyurea prevents DNA synthesis by depleting nucleotide pools (Young and Hodas, 1964). Because adequate nucleotide pools must be available before DNA elongation can begin, hydroxyurea should block S-phase at an earlier time point than aphidicolin.…”

Section: Aphidicolin Inhibits Viral Dna Synthesismentioning

confidence: 99%

Host DNA Replication Is Induced by Geminivirus Infection of Differentiated Plant Cells

2002

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The geminivirus Tomato golden mosaic virus (TGMV) replicates in differentiated plant cells using host DNA synthesis machinery. We used 5-bromo-2-deoxyuridine (BrdU) incorporation to examine DNA synthesis directly in infected Nicotiana benthamiana plants to determine if viral reprogramming of host replication controls had an impact on host DNA replication. Immunoblot analysis revealed that up to 17-fold more BrdU was incorporated into chromosomal DNA of TGMV-infected versus mock-infected, similarly treated healthy leaves. Colocalization studies of viral DNA and BrdU demonstrated that BrdU incorporation was specific to infected cells and was associated with both host and viral DNA. TGMV and host DNA synthesis were inhibited differentially by aphidicolin but were equally sensitive to hydroxyurea. Short BrdU labeling times resulted in some infected cells showing punctate foci associated with host DNA. Longer periods showed BrdU label uniformly throughout host DNA, some of which showed condensed chromatin, only in infected nuclei. By contrast, BrdU associated with viral DNA was centralized and showed uniform, compartmentalized labeling. Our results demonstrate that chromosomal DNA is replicated in TGMV-infected cells.

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Section: Aphidicolin Inhibits Viral Dna Synthesismentioning

confidence: 99%

Host DNA Replication Is Induced by Geminivirus Infection of Differentiated Plant Cells

2002

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“…Zunächst wurde der Einfluß steigender Hydroxyharnstoffkonzentrationen auf den Einbau von 3 finden sich während der ersten Stunden knapp über 70% der Gesamtpopulation in der S-Phase. Da bei den Kontrollen bereits 35% der Zellen in der S-Phase sind und diese bei Zugabe von HH zum Kulturmedium sofort in ihrer Proliferation gehemmt werden, müssen sie für eine exakte Synchronisation zunächst aus der S-Phase entfernt werden.…”

Section: Ergebnisseunclassified

Die Wirkung von Hydroxyharnstoff auf die DNA-Synthese embryonaler Rattenzellen in Kultur / The Effect of Hydroxyurea on DNA Synthesis of Embryonic Rat Cells in Culture

Manso-Martínez

Frank

1972

Zeitschrift Für Naturforschung B

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3H-thymidine incorporation by secondary cultures of embryonic rat cells and by cultures of a permanent rat cell line is strongly inhibited a few minutes after addition of hydroxyurea (HU) to the culture medium (2 × 10-3 ᴍ and 5 × 10-4 ᴍ, resp.); normal embryonic rat cells are considerably less sensitive to the drug than are permanent cells. About 76 percent of the population of a secondary culture can be synchronized at the beginning of the S-period, if the cells at first are accumulated in G1 phase by incubation in serum-free medium and subsequently are stimulated by the addition of ten percent calf serum in the presence of 2 × 10-3 ᴍ HU.The size of DNA replicated in the presence of HU has been analysed by centrifugation in alkaline sucrose gradients. The results indicate that under these conditions DNA subunits are synthesized with sedimentation coefficients between 21S and 30S. These intermediates cannot be joined together, probably because a ligase is inhibited by HU.Secondary culture incubated in medium-containing 1 × 10-4 ᴍ HU incorporate twice as much 3H-thymidine as do control cells in HU-free medium. This is due to an increased number of cells in the S phase, as was shown by autoradiography. The kinetics of thymidine incorporation indicate that the duration of G1 phase is shortened by small doses of HU

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“…30 This reversibly blocks the replication fork in S-phase and may also cause DNA fragmentation and chromosomal abnormalities. 30,31 If the putative Arabidopsis CDC25 gene has the conserved Cdc25 function, we expected that overexpressing plants should show hypersensitivity towards genotoxic stress similar to the situation in human cells. 12,32 However, neither the gainnor the loss-of-function mutants showed a phenotype distinguishable from the wild type (Fig.…”

Section: Assessing the Function Of The Putative Arabidopsis Cdc25 Undmentioning

confidence: 99%

The regulatory network of cell-cycle progression is fundamentally different in plants versus yeast or metazoans

Dißmeyer

Weimer

Veylder

et al. 2010

Plant Signaling & Behavior

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Hydroxyurea: Inhibitory Effect on DNA Metabolism

Cited by 398 publications

References 7 publications

Host DNA Replication Is Induced by Geminivirus Infection of Differentiated Plant Cells

Host DNA Replication Is Induced by Geminivirus Infection of Differentiated Plant Cells

Die Wirkung von Hydroxyharnstoff auf die DNA-Synthese embryonaler Rattenzellen in Kultur / The Effect of Hydroxyurea on DNA Synthesis of Embryonic Rat Cells in Culture

The regulatory network of cell-cycle progression is fundamentally different in plants versus yeast or metazoans

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