{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:09:43Z","timestamp":1781716183323,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,2,5]],"date-time":"2005-02-05T00:00:00Z","timestamp":1107561600000},"content-version":"vor","delay-in-days":4298,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[1993,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including <jats:italic>E. coli, S. cerevisiae<\/jats:italic> and <jats:italic>H. sapiens<\/jats:italic>. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. <jats:italic>S. cerevisiae<\/jats:italic> also encodes a second large subunit gene, <jats:italic>RNR3<\/jats:italic>, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in <jats:italic>S. cerevisiae<\/jats:italic> has shown that <jats:italic>RNR<\/jats:italic> expression is under both positive and negative control. Among mutants constitutive for <jats:italic>RNR<\/jats:italic> expression are the general transcriptional repression genes, <jats:italic>SSN6<\/jats:italic> and <jats:italic>TUP1<\/jats:italic>. Mutations in <jats:italic>POL1<\/jats:italic> and <jats:italic>POL3<\/jats:italic> also activate <jats:italic>RNR<\/jats:italic> expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of <jats:italic>RNR1, RNR2<\/jats:italic> and <jats:italic>RNR3<\/jats:italic> in response to DNA damage and replication blocks. This result suggests that the <jats:italic>RNR<\/jats:italic> genes in <jats:italic>S. cerevisiae<\/jats:italic> form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage.<\/jats:p>","DOI":"10.1002\/bies.950150507","type":"journal-article","created":{"date-parts":[[2005,2,25]],"date-time":"2005-02-25T09:26:11Z","timestamp":1109323571000},"page":"333-339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":192,"title":["DNA damage and cell cycle regulation of ribonucleotide reductase"],"prefix":"10.1002","volume":"15","author":[{"given":"Stephen J.","family":"Elledge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony A.","family":"Navas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,2,5]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950140502"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"7066","DOI":"10.1016\/S0021-9258(19)50537-3","article-title":"Alterations in the activity and regulation of mammalian ribonucleotide reductase by chlorambucil, a DNA damaging agent","volume":"267","author":"Hurta R. 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