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Gene Review

RNR3  -  ribonucleotide-diphosphate reductase...

Saccharomyces cerevisiae S288c

Synonyms: DIN1, RIR3, Ribonucleoside-diphosphate reductase large chain 2, Ribonucleotide reductase DNA damage-inducible regulatory subunit 2, Ribonucleotide reductase R1 subunit 2, ...
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Disease relevance of RNR3


High impact information on RNR3

  • We investigated the mechanism by which DNA damage induces transcription of RNR3, a subunit of ribonucleotide reductase [3].
  • Inactivation of this domain abolished DNA damage-dependent Rad53 phosphorylation, G2/M cell cycle phase arrest, and increase of RNR3 transcription but did not affect replication inhibition-dependent Rad53 phosphorylation [4].
  • SWI/SNF-dependent chromatin remodeling of RNR3 requires TAF(II)s and the general transcription machinery [5].
  • Examination of the inducibility of RNR3 in response to UV damage has revealed that the various checkpoint genes can be arranged in a pathway consistent with their requirement to arrest cells at different stages of the cell cycle [6].
  • RNR1 is inducible 3- to 5-fold, and RNR3 is inducible greater than 100-fold [7].

Biological context of RNR3

  • Mutants defective for both pathways are severely deficient in Rad53p phosphorylation and RNR3 induction and are significantly more sensitive to DNA damage and replication blocks than single mutants alone [6].
  • Yet an rnr3 null mutant has no obvious phenotype even under DNA damaging conditions, and the contribution of RNR3 to ribonucleotide reduction is not clear [8].
  • To probe the signaling pathway mediating this DNA damage response, we have designed a general selection system for isolating spontaneous trans-acting mutations that alter RNR3 expression using a chromosomal RNR3-URA3 transcriptional fusion and an RNR3-lacZ reporter plasmid [9].
  • When MATa cells are arrested in G1 by alpha-factor, RNR1 and RNR3 mRNA is still inducible by DNA damage, indicating that the observed induction can occur outside of S phase [7].
  • At earlier stages of growth, as the telomerase-deficient cells began to show loss of growth potential, the cells arrested in G2/M and showed RNR3 induction and Rad53p phosphorylation [10].

Associations of RNR3 with chemical compounds


Regulatory relationships of RNR3

  • Yeast DNA damage-inducible Rnr3 has a very low catalytic activity strongly stimulated after the formation of a cross-talking Rnr1/Rnr3 complex [8].
  • Furthermore, Tup1 repressed RNR3 and blocked preinitiation complex formation in the Deltaisw2 mutant, even though nucleosome positioning was completely disrupted over the promoter and ORF [13].

Other interactions of RNR3

  • Previous work has identified two genes in the yeast Saccharomyces cerevisiae, RNR1 and RNR3, that encode alpha subunits and one gene, RNR2, that encodes a beta subunit [14].
  • The lethality of RNR4 deletion mutations can be suppressed by overexpression of RNR1 and RNR3, two genes encoding the large subunit of the RNR enzyme, indicating genetic interactions among the RNR genes [15].
  • Furthermore, the inducibility of RNR3 transcription in response to DNA damage is dependent on RFC5 [16].
  • The in vitro activity of Rnr3 was less than 1% of the Rnr1 activity [8].
  • Here, we demonstrate that both ISW2 and TUP1 are required to position nucleosomes across the entire coding sequence of the DNA damage-inducible gene RNR3 [13].

Analytical, diagnostic and therapeutic context of RNR3


  1. Ccr4 contributes to tolerance of replication stress through control of CRT1 mRNA poly(A) tail length. Woolstencroft, R.N., Beilharz, T.H., Cook, M.A., Preiss, T., Durocher, D., Tyers, M. J. Cell. Sci. (2006) [Pubmed]
  2. Development of RNR3- and RAD54-GUS reporters for testing genotoxicity in Saccharomyces cerevisiae. Boronat, S., Pi??a, B. Analytical and bioanalytical chemistry (2006) [Pubmed]
  3. DUN1 encodes a protein kinase that controls the DNA damage response in yeast. Zhou, Z., Elledge, S.J. Cell (1993) [Pubmed]
  4. Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. Sun, Z., Hsiao, J., Fay, D.S., Stern, D.F. Science (1998) [Pubmed]
  5. SWI/SNF-dependent chromatin remodeling of RNR3 requires TAF(II)s and the general transcription machinery. Sharma, V.M., Li, B., Reese, J.C. Genes Dev. (2003) [Pubmed]
  6. RAD9 and DNA polymerase epsilon form parallel sensory branches for transducing the DNA damage checkpoint signal in Saccharomyces cerevisiae. Navas, T.A., Sanchez, Y., Elledge, S.J. Genes Dev. (1996) [Pubmed]
  7. Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase. Elledge, S.J., Davis, R.W. Genes Dev. (1990) [Pubmed]
  8. Yeast DNA damage-inducible Rnr3 has a very low catalytic activity strongly stimulated after the formation of a cross-talking Rnr1/Rnr3 complex. Domkin, V., Thelander, L., Chabes, A. J. Biol. Chem. (2002) [Pubmed]
  9. Isolation of crt mutants constitutive for transcription of the DNA damage inducible gene RNR3 in Saccharomyces cerevisiae. Zhou, Z., Elledge, S.J. Genetics (1992) [Pubmed]
  10. Short telomeres induce a DNA damage response in Saccharomyces cerevisiae. IJpma, A.S., Greider, C.W. Mol. Biol. Cell (2003) [Pubmed]
  11. Role of the putative zinc finger domain of Saccharomyces cerevisiae DNA polymerase epsilon in DNA replication and the S/M checkpoint pathway. Dua, R., Levy, D.L., Campbell, J.L. J. Biol. Chem. (1998) [Pubmed]
  12. Induction in the gene RNR3 in Saccharomyces cerevisiae upon exposure to different agents related to carcinogenesis. Endo-Ichikawa, Y., Kohno, H., Tokunaga, R., Taketani, S. Biochem. Pharmacol. (1995) [Pubmed]
  13. Ssn6-Tup1 requires the ISW2 complex to position nucleosomes in Saccharomyces cerevisiae. Zhang, Z., Reese, J.C. EMBO J. (2004) [Pubmed]
  14. Rnr4p, a novel ribonucleotide reductase small-subunit protein. Wang, P.J., Chabes, A., Casagrande, R., Tian, X.C., Thelander, L., Huffaker, T.C. Mol. Cell. Biol. (1997) [Pubmed]
  15. Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae. Huang, M., Elledge, S.J. Mol. Cell. Biol. (1997) [Pubmed]
  16. Rfc5, a replication factor C component, is required for regulation of Rad53 protein kinase in the yeast checkpoint pathway. Sugimoto, K., Ando, S., Shimomura, T., Matsumoto, K. Mol. Cell. Biol. (1997) [Pubmed]
  17. Effects of modifying topoisomerase II levels on cellular recovery from radiation damage. Gaffney, D.K., Lundquist, M., Warters, R.L., Rosley, R. Radiat. Res. (2000) [Pubmed]
  18. DNA damage and replication stress induced transcription of RNR genes is dependent on the Ccr4-Not complex. Mulder, K.W., Winkler, G.S., Timmers, H.T. Nucleic Acids Res. (2005) [Pubmed]
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