2004
DOI: 10.1074/jbc.m303952200
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Abstract: The relationship between dNTP levels and DNA synthesis was investigated using ␣ factor-synchronized yeast treated with the ribonucleotide reductase inhibitor hydroxyurea (HU). Although HU blocked DNA synthesis and prevented the dNTP pool expansion that normally occurs at G 1 /S, it did not exhaust the levels of any of the four dNTPs, which dropped to about 80% of G 1 levels. When dbf4 yeast that are ts for replication initiation were allowed to preaccumulate dNTPs at 37°C before being released to 25°C in the p… Show more

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Cited by 330 publications
(179 citation statements)
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“…This results in inhibition of S phase and causes stalled replication forks (Koç et al, 2004). ARTD10 knockdown cells are more sensitive to HU-induced DNA damage as the catalytic activity is necessary for its DNA repair functions (Nicolae et al, 2014).…”
Section: Hydroxyurea Sensitivity Confirms the Role Of Artd10 In Genotmentioning
confidence: 99%
“…This results in inhibition of S phase and causes stalled replication forks (Koç et al, 2004). ARTD10 knockdown cells are more sensitive to HU-induced DNA damage as the catalytic activity is necessary for its DNA repair functions (Nicolae et al, 2014).…”
Section: Hydroxyurea Sensitivity Confirms the Role Of Artd10 In Genotmentioning
confidence: 99%
“…During conditions of DNA damage, DNA replication requires a further increase in dNTP levels to promote efficient repair synthesis. 11,12 The survival of S. cerevisiae in response to DNA damaging agents has been previously shown to depend on increased dNTP levels. 13 Hence, factors that reduce dNTP levels, by reducing Rnr1, Rnr2 and Rnr4 levels or RNR activity, render cells hypersensitive to DNA damaging agents as well as to the RNR inhibitor hydroxyurea (HU).…”
Section: Introductionmentioning
confidence: 99%
“…The effect of hydroxyurea against Leishmania mexicana was shown to be more effective than that against Plasmodium falciparum, which has an ED 50 of 792 M (18), and to have a 50% inhibitory dose for antitumor activity in vitro of 500 M (13). Hydroxyurea reportedly affects the cell cycle by arresting the G 1 phase-S phase (20,34), characterized by DNA replication, in Saccharomyces cerevisiae yeasts (20), vascular smooth muscle cells (4), and Leishmania major (34). Inhibition of DNA synthesis by inhibition of an enzyme, ribonucleotide reductase, represents the most probable explanation for the mechanism by which hydroxyurea inhibits the parasite at this level (26).…”
Section: Discussionmentioning
confidence: 99%