RNR1

Summary

Gene Symbol: RNR1
Description: ribonucleotide-diphosphate reductase subunit RNR1
Alias: CRT7, RIR1, SDS12, ribonucleotide-diphosphate reductase subunit RNR1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Elledge S, Davis R. Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase. Genes Dev. 1990;4:740-51 pubmed
    ..and characterized two Saccharomyces cerevisiae genes encoding the regulatory subunit of ribonucleotide reductase, RNR1 and RNR3. They share approximately 80% amino acid identity with each other and 60% with the mammalian homolog, M1...
  2. Huang M, Elledge S. Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae. Mol Cell Biol. 1997;17:6105-13 pubmed
    ..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 ..
  3. Huang M, Zhou Z, Elledge S. The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Cell. 1998;94:595-605 pubmed
    ..The inhibition of an autoregulatory repressor in response to DNA damage is a strategy conserved throughout prokaryotic and eukaryotic evolution. ..
  4. Zhang Z, Yang K, Chen C, Feser J, Huang M. Role of the C terminus of the ribonucleotide reductase large subunit in enzyme regeneration and its inhibition by Sml1. Proc Natl Acad Sci U S A. 2007;104:2217-22 pubmed
    ..These results point to a model whereby Sml1 competes with R1-CTD for association with R1-NTD to hinder the accessibility of the CX2C motif to the active site for R1 regeneration. ..
  5. Woolstencroft R, Beilharz T, Cook M, Preiss T, Durocher D, Tyers M. Ccr4 contributes to tolerance of replication stress through control of CRT1 mRNA poly(A) tail length. J Cell Sci. 2006;119:5178-92 pubmed
    ..These results implicate the coordinated regulation of Crt1 via Ccr4 and Dun1 as a crucial nodal point in the response to DNA replication stress. ..
  6. Desany B, Alcasabas A, Bachant J, Elledge S. Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway. Genes Dev. 1998;12:2956-70 pubmed
    ..We propose that this checkpoint pathway plays an important role in the maintenance of DNA synthetic capabilities when DNA replication is stressed. ..
  7. Chabes A, Domkin V, Thelander L. Yeast Sml1, a protein inhibitor of ribonucleotide reductase. J Biol Chem. 1999;274:36679-83 pubmed
    ..A novel protein, Sml1, was shown to bind to the Rnr1 protein of the yeast ribonucleotide reductase; this interaction was proposed to inhibit ribonucleotide reductase ..
  8. Zhao X, Muller E, Rothstein R. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Mol Cell. 1998;2:329-40 pubmed
    ..sml1 affects various cellular processes analogous to overproducing the large subunit of ribonucleotide reductase, RNR1. These include effects on mitochondrial biogenesis, on the DNA damage response, and on cell growth...
  9. Koren A, Soifer I, Barkai N. MRC1-dependent scaling of the budding yeast DNA replication timing program. Genome Res. 2010;20:781-90 pubmed publisher
    ..Mrc1 emerges as a regulator of this robustness of the replication program. ..

More Information

Publications52

  1. Kumar D, Viberg J, Nilsson A, Chabes A. Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint. Nucleic Acids Res. 2010;38:3975-83 pubmed publisher
    ..In contrast, when none of the dNTPs was limiting for DNA replication, even extreme and mutagenic dNTP pool imbalances did not activate the S-phase checkpoint and did not interfere with the cell cycle progression. ..
  2. Yao R, Zhang Z, An X, Bucci B, Perlstein D, Stubbe J, et al. Subcellular localization of yeast ribonucleotide reductase regulated by the DNA replication and damage checkpoint pathways. Proc Natl Acad Sci U S A. 2003;100:6628-33 pubmed
    ..In Saccharomyces cerevisiae, there are two large subunits (Rnr1 and Rnr3) and two small subunits (Rnr2 and Rnr4)...
  3. Chabes A, Stillman B. Constitutively high dNTP concentration inhibits cell cycle progression and the DNA damage checkpoint in yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2007;104:1183-8 pubmed
    ..We propose that fluctuation of dNTP concentration controls cell cycle progression and the initiation of DNA replication. ..
  4. Chabes A, Domkin V, Larsson G, Liu A, Graslund A, Wijmenga S, et al. Yeast ribonucleotide reductase has a heterodimeric iron-radical-containing subunit. Proc Natl Acad Sci U S A. 2000;97:2474-9 pubmed
    ..Taken together, our results show that the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit. ..
  5. Zhao X, Rothstein R. The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1. Proc Natl Acad Sci U S A. 2002;99:3746-51 pubmed
    ..Finally, Dun1 can phosphorylate Sml1 in vitro. These results suggest that Dun1 kinase function is the last step required in the Mec1/Rad53 cascade to remove Sml1 during S phase and after DNA damage. ..
  6. Domkin V, Thelander L, Chabes A. Yeast DNA damage-inducible Rnr3 has a very low catalytic activity strongly stimulated after the formation of a cross-talking Rnr1/Rnr3 complex. J Biol Chem. 2002;277:18574-8 pubmed
    The ribonucleotide reductase system in Saccharomyces cerevisiae includes four genes (RNR1 and RNR3 encoding the large subunit and RNR2 and RNR4 encoding the small subunit)...
  7. Zhao X, Georgieva B, Chabes A, Domkin V, Ippel J, Schleucher J, et al. Mutational and structural analyses of the ribonucleotide reductase inhibitor Sml1 define its Rnr1 interaction domain whose inactivation allows suppression of mec1 and rad53 lethality. Mol Cell Biol. 2000;20:9076-83 pubmed
    ..lethality is suppressed by removal of Sml1, a protein that binds to the large subunit of ribonucleotide reductase (Rnr1) and inhibits RNR activity...
  8. Xu H, Faber C, Uchiki T, Fairman J, Racca J, Dealwis C. Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation. Proc Natl Acad Sci U S A. 2006;103:4022-7 pubmed
    ..In eukaryotes, the enzyme comprises a heterooligomer of alpha(2) and beta(2) subunits. The alpha subunit, Rnr1, contains catalytic and regulatory sites...
  9. Fikus M, Mieczkowski P, Koprowski P, Rytka J, Sledziewska Gojska E, Ciesla Z. The product of the DNA damage-inducible gene of Saccharomyces cerevisiae, DIN7, specifically functions in mitochondria. Genetics. 2000;154:73-81 pubmed
    ..We have found that dun1 strains, defective in the transcriptional activation of the DNA damage-inducible genes RNR1, RNR2, and RNR3, exhibit an increased frequency in the formation of the mitochondrial petite (rho(-)) mutants...
  10. Amin N, Nguyen M, Oh S, Kolodner R. exo1-Dependent mutator mutations: model system for studying functional interactions in mismatch repair. Mol Cell Biol. 2001;21:5142-55 pubmed
    ..exo1 mutation, exo1-dependent mutator mutations were obtained in MLH1, PMS1, MSH2, MSH3, POL30 (PCNA), POL32, and RNR1, whereas starting with the weak pms1 allele pms1-A130V, pms1-dependent mutator mutations were identified in MLH1, ..
  11. Misko T, Wijerathna S, Radivoyevitch T, Berdis A, Ahmad M, Harris M, et al. Inhibition of yeast ribonucleotide reductase by Sml1 depends on the allosteric state of the enzyme. FEBS Lett. 2016;590:1704-12 pubmed publisher
    ..Gel filtration and mutagenesis studies indicate that Sml1 does not alter the oligomerization equilibrium and the CXXC motif is not involved in the inhibition. The data suggest that Sml1 is an allosteric inhibitor. ..
  12. Vitols E, Bauer V, Stanbrough E. Ribonucleotide reductase from Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1970;41:71-7 pubmed
  13. Lebedeva M, Shadel G. Cell cycle- and ribonucleotide reductase-driven changes in mtDNA copy number influence mtDNA Inheritance without compromising mitochondrial gene expression. Cell Cycle. 2007;6:2048-57 pubmed
    ..strains leads to defective mtDNA inheritance that is partially rescued by replenishing mtDNA via overexpression of RNR1. These results indicate that one role for multiple mtDNA copies is to ensure optimal inheritance of mtDNA during ..
  14. Baruffini E, Lodi T, Dallabona C, Puglisi A, Zeviani M, Ferrero I. Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans. Hum Mol Genet. 2006;15:2846-55 pubmed
    ..effects of pol gamma mutations in yeast, we have overexpressed a dNTP checkpoint enzyme, ribonucleotide reductase, RNR1, or deleted its inhibitor, SML1. In both mutant strains, the petite mutability was dramatically reduced...
  15. Biswas D, Takahata S, Xin H, Dutta Biswas R, Yu Y, Formosa T, et al. A role for Chd1 and Set2 in negatively regulating DNA replication in Saccharomyces cerevisiae. Genetics. 2008;178:649-59 pubmed publisher
    ..The pob3 defect in S-phase progression is suppressed by set2 or chd1 mutations, suggesting that Set2 and Chd1 have specific roles in negatively regulating DNA replication. ..
  16. Buckland R, Watt D, Chittoor B, Nilsson A, Kunkel T, Chabes A. Increased and imbalanced dNTP pools symmetrically promote both leading and lagging strand replication infidelity. PLoS Genet. 2014;10:e1004846 pubmed publisher
    ..by examining strand-specific replication infidelity driven by a mutation in yeast ribonucleotide reductase, rnr1-Y285A, that leads to elevated dTTP and dCTP concentrations...
  17. Laman H, Balderes D, Shore D. Disturbance of normal cell cycle progression enhances the establishment of transcriptional silencing in Saccharomyces cerevisiae. Mol Cell Biol. 1995;15:3608-17 pubmed
    ..b>SDS12 is identical to RNR1, which encodes a subunit of ribonucleotide reductase...
  18. Nguyen H, Ge J, Perlstein D, Stubbe J. Purification of ribonucleotide reductase subunits Y1, Y2, Y3, and Y4 from yeast: Y4 plays a key role in diiron cluster assembly. Proc Natl Acad Sci U S A. 1999;96:12339-44 pubmed
    ..Class I RNRs are composed of two types of subunits: RNR1 contains the active site for reduction and the binding sites for the nucleotide allosteric effectors...
  19. Tai A, Kamei Y, Mukai Y. The forkhead-like transcription factor (Fhl1p) maintains yeast replicative lifespan by regulating ribonucleotide reductase 1 (RNR1) gene transcription. Biochem Biophys Res Commun. 2017;488:218-223 pubmed publisher
    ..We identified the ribonucleotide reductase (RNR) 1 gene (RNR1) as a regulator of replicative lifespan...
  20. Jay K, Smith D, Blackburn E. Early Loss of Telomerase Action in Yeast Creates a Dependence on the DNA Damage Response Adaptor Proteins. Mol Cell Biol. 2016;36:1908-19 pubmed publisher
    ..We propose that normally occurring telomeric DNA replication stress is resolved by telomerase activity and the DDR in two parallel pathways and that deletion of Sml1 prevents this stress. ..
  21. Betz J, Chang M, Washburn T, Porter S, Mueller C, Jaehning J. Phenotypic analysis of Paf1/RNA polymerase II complex mutations reveals connections to cell cycle regulation, protein synthesis, and lipid and nucleic acid metabolism. Mol Genet Genomics. 2002;268:272-85 pubmed
    ..For example, paf1 Delta causes sensitivity to hydroxyurea; this phenotype correlates with a reduction in RNR1 transcript abundance and is suppressed by over-expression of RNR1...
  22. Tsaponina O, Barsoum E, Aström S, Chabes A. Ixr1 is required for the expression of the ribonucleotide reductase Rnr1 and maintenance of dNTP pools. PLoS Genet. 2011;7:e1002061 pubmed publisher
    ..Among the genes repressed by Crt1 are three out of four RNR genes: RNR2, RNR3, and RNR4. The fourth RNR gene, RNR1, is also DNA damage-inducible, but is not controlled by Crt1...
  23. Vallen E, Cross F. Interaction between the MEC1-dependent DNA synthesis checkpoint and G1 cyclin function in Saccharomyces cerevisiae. Genetics. 1999;151:459-71 pubmed
    ..We identified RNR1, which encodes a subunit of ribonucleotide reductase, as a high-copy suppressor of the lethality of mec1 GAL1-CLN1...
  24. Dhillon N, Oki M, Szyjka S, Aparicio O, Kamakaka R. H2A.Z functions to regulate progression through the cell cycle. Mol Cell Biol. 2006;26:489-501 pubmed
    ..We also found that H2A.Z localized to the promoters of cyclin genes, and cells lacking H2A.Z were delayed in the induction of these cyclin genes. Several different models are proposed to explain these observations. ..
  25. Zhang Y, An X, Stubbe J, Huang M. Investigation of in vivo roles of the C-terminal tails of the small subunit (??') of Saccharomyces cerevisiae ribonucleotide reductase: contribution to cofactor formation and intersubunit association within the active holoenzyme. J Biol Chem. 2013;288:13951-9 pubmed publisher
  26. Andreson B, Gupta A, Georgieva B, Rothstein R. The ribonucleotide reductase inhibitor, Sml1, is sequentially phosphorylated, ubiquitylated and degraded in response to DNA damage. Nucleic Acids Res. 2010;38:6490-501 pubmed publisher
    ..Further, in a strain containing a mutation in Rnr1, rnr1-W688G, mutation of these sites in Sml1 causes lethality...
  27. Marsolier M, Roussel P, Leroy C, Mann C. Involvement of the PP2C-like phosphatase Ptc2p in the DNA checkpoint pathways of Saccharomyces cerevisiae. Genetics. 2000;154:1523-32 pubmed
    ..Deleting PTC2 specifically suppresses the hydroxyurea hypersensitivity of mec1 mutants and the lethality of mec1Delta. PTC2 is thus implicated in one or several functions related to RAD53, MEC1, and the DNA checkpoint pathways. ..
  28. Smith R, Wellman K, Smith M. Trans-species activity of a nonself recognition domain. BMC Microbiol. 2013;13:63 pubmed publisher
    ..Finally, our results suggest that variations on the PA incompatibility domain may serve as novel and specific antimicrobial peptides. ..
  29. Xu H, Faber C, Uchiki T, Racca J, Dealwis C. Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly. Proc Natl Acad Sci U S A. 2006;103:4028-33 pubmed
    ..In eukaryotes, RNR comprises a heterooligomer of alpha(2) and beta(2) subunits. Rnr1, the alpha subunit, contains regulatory and catalytic sites; Rnr2, the beta subunit (in yeast, a heterodimer of ..
  30. Hu F, Alcasabas A, Elledge S. Asf1 links Rad53 to control of chromatin assembly. Genes Dev. 2001;15:1061-6 pubmed
    ..Thus, checkpoint pathways directly regulate chromatin assembly to promote survival in response to DNA damage and replication blocks. ..
  31. Lecrenier N, Foury F. Overexpression of the RNR1 gene rescues Saccharomyces cerevisiae mutants in the mitochondrial DNA polymerase-encoding MIP1 gene. Mol Gen Genet. 1995;249:1-7 pubmed
    ..mutants in the mitochondrial DNA (mtDNA) polymerase-encoding MIP1 gene has been isolated and identified as the RNR1 gene...
  32. Rubinstein L, Ungar L, Harari Y, Babin V, Ben Aroya S, Merenyi G, et al. Telomere length kinetics assay (TELKA) sorts the telomere length maintenance (tlm) mutants into functional groups. Nucleic Acids Res. 2014;42:6314-25 pubmed publisher
    ..unknown MET7 gene has the same telomeric kinetics as mutants defective for the ribonucleotide reductase subunit Rnr1, in charge of the limiting step in dNTP synthesis, or for the Ku heterodimer, a well-established telomere complex...
  33. Nestoras K, Mohammed A, Schreurs A, Fleck O, Watson A, Poitelea M, et al. Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms. Genes Dev. 2010;24:1145-59 pubmed publisher
    ..Finally, we identify a new behavior for RNR complexes that potentially provides yet another mechanism to regulate dNTP synthesis via modulation of RNR complex architecture. ..
  34. Patil A, Dyavaiah M, Joseph F, Rooney J, Chan C, Dedon P, et al. Increased tRNA modification and gene-specific codon usage regulate cell cycle progression during the DNA damage response. Cell Cycle. 2012;11:3656-65 pubmed publisher
    S-phase and DNA damage promote increased ribonucleotide reductase (RNR) activity. Translation of RNR1 has been linked to the wobble uridine modifying enzyme tRNA methyltransferase 9 (Trm9)...
  35. Dyavaiah M, Rooney J, Chittur S, Lin Q, Begley T. Autophagy-dependent regulation of the DNA damage response protein ribonucleotide reductase 1. Mol Cancer Res. 2011;9:462-75 pubmed publisher
    ..Significantly, we demonstrate that two transcriptionally-induced DNA damage response genes, RNR1 and RNR4, fail to show soluble protein level increases after DNA damage...
  36. Mao G, Brody J. Reverse engineering the yeast RNR1 transcriptional control system. PLoS ONE. 2010;5:e13895 pubmed publisher
    ..A major goal of modern biology is to provide simple models that predict this complex behavior. The yeast gene RNR1 is transcribed periodically during the cell cycle...
  37. Lee R, Brunette S, Puente L, Megeney L. Metacaspase Yca1 is required for clearance of insoluble protein aggregates. Proc Natl Acad Sci U S A. 2010;107:13348-53 pubmed publisher
    ..Together, our results show that Yca1 contributes to the fitness and adaptability of growing yeast through an aggregate remodeling activity. ..
  38. Ahmad M, Kaushal P, Wan Q, Wijerathna S, An X, Huang M, et al. Role of arginine 293 and glutamine 288 in communication between catalytic and allosteric sites in yeast ribonucleotide reductase. J Mol Biol. 2012;419:315-29 pubmed publisher
    ..Taken together, our structure, activity, ITC and in vivo data reveal that the arginine 293 and glutamine 288 residues of ScRR1 are crucial in facilitating ADP and CDP substrate selection. ..
  39. Weinberger M, Sampaio Marques B, Ludovico P, Burhans W. DNA replication stress-induced loss of reproductive capacity in S. cerevisiae and its inhibition by caloric restriction. Cell Cycle. 2013;12:1189-200 pubmed publisher
    ..Overexpression of RNR1 encoding a ribonucleotide reductase subunit required for the synthesis of deoxynucleotide triphosphates and DNA ..
  40. Gardner R, Putnam C, Weinert T. RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. EMBO J. 1999;18:3173-85 pubmed
    ..Instead, we think it likely that both pathways contribute to establishing and maintaining arrest. ..
  41. Schroeder E, Shadel G. Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan. Mech Ageing Dev. 2014;135:41-9 pubmed publisher
  42. Dosil M. Ribosome synthesis-unrelated functions of the preribosomal factor Rrp12 in cell cycle progression and the DNA damage response. Mol Cell Biol. 2011;31:2422-38 pubmed publisher
    ..I propose that the functional duality of Rrp12 may couple the control of ribosome production to the regulation of other cellular processes during cell cycle progression. ..
  43. O Rourke T, Doudican N, Zhang H, Eaton J, Doetsch P, Shadel G. Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stability. Gene. 2005;354:86-92 pubmed
    ..In addition, we found that over-expression of RNR1, encoding a large subunit of ribonucleotide reductase (RNR), rescued the petite-induction phenotype of a pif1Delta ..