Gene Symbol: RnrS
Description: Ribonucleoside diphosphate reductase small subunit
Alias: CG8975, DmRNR2, Dmel\CG8975, RNR2, RNRS, RNrS, Rnr2, Rnrs, anon-WO0118547.148, dRNR2, rnr2, rnrS, ribonucleoside diphosphate reductase small subunit, CG8975-PA, RnrS-PA, ribonucleoside-diphosphate reductase small subunit, ribonucleotide reductase, ribonucleotide reductase small subunit
Species: fruit fly

Top Publications

  1. Moon N, Frolov M, Kwon E, Di Stefano L, Dimova D, Morris E, et al. Drosophila E2F1 has context-specific pro- and antiapoptotic properties during development. Dev Cell. 2005;9:463-75 pubmed
    ..These loss-of-function experiments demonstrate that E2F cannot be classified simply as a pro- or antiapoptotic factor. Instead, the overall role of E2F in the damage response varies greatly and depends on the cellular context. ..
  2. Shibutani S, Swanhart L, Duronio R. Rbf1-independent termination of E2f1-target gene expression during early Drosophila embryogenesis. Development. 2007;134:467-78 pubmed
    ..Here we show that the initial downregulation of expression of the E2f1-target gene RnrS, which occurs during cycles 15 and 16 prior to entry into G1(17), does not require Rbf1 or p27(Dap)...
  3. Duronio R, Brook A, Dyson N, O Farrell P. E2F-induced S phase requires cyclin E. Genes Dev. 1996;10:2505-13 pubmed
    ..Mutation of cyclin E prevented the initiation of S phase after overexpression of dE2F/dDP without affecting induction of target gene expression. Thus, E2F-directed transcription cannot bypass loss of cyclin E in Drosophila embryos. ..
  4. Duronio R, O Farrell P. Developmental control of the G1 to S transition in Drosophila: cyclin Eis a limiting downstream target of E2F. Genes Dev. 1995;9:1456-68 pubmed
  5. Frolov M, Moon N, Dyson N. dDP is needed for normal cell proliferation. Mol Cell Biol. 2005;25:3027-39 pubmed
    ..Thus, dDP is not essential for developmental control of the G1-to-S transition, but it is required for normal cell proliferation, for optimal DNA synthesis, and for efficient G2/M progression. ..
  6. Shibutani S, de la Cruz A, Tran V, Turbyfill W, Reis T, Edgar B, et al. Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev Cell. 2008;15:890-900 pubmed publisher
    ..We propose that pRb-independent inhibition of E2F during S phase is an evolutionarily conserved feature of the metazoan cell cycle that is necessary for development. ..
  7. Royzman I, Austin R, Bosco G, Bell S, Orr Weaver T. ORC localization in Drosophila follicle cells and the effects of mutations in dE2F and dDP. Genes Dev. 1999;13:827-40 pubmed
    ..The effect of the mutations in the heterodimer subunits suggests that E2F controls not only the onset of S phase but also origin activity within S phase. ..
  8. Du W, Dyson N. The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis. EMBO J. 1999;18:916-25 pubmed
    ..Embryos lacking both maternal and zygotic RBF products show constitutive expression of PCNA and RNR2, two E2F-regulated genes, indicating that RBF is required for their transcriptional repression...
  9. Moon N, Di Stefano L, Dyson N. A gradient of epidermal growth factor receptor signaling determines the sensitivity of rbf1 mutant cells to E2F-dependent apoptosis. Mol Cell Biol. 2006;26:7601-15 pubmed
    ..These results demonstrate that a gradient of DER/ras/raf signaling that occurs naturally during development provides the contextual signals that determine when and where the inactivation of rbf1 results in dE2F1-dependent apoptosis. ..

More Information


  1. Duronio R, O Farrell P, Xie J, Brook A, Dyson N. The transcription factor E2F is required for S phase during Drosophila embryogenesis. Genes Dev. 1995;9:1445-55 pubmed
    ..We conclude that in most cells dE2F is essential for a G1-S transcriptional program and for G1-S progression. ..
  2. Moon N, Di Stefano L, Morris E, Patel R, White K, Dyson N. E2F and p53 induce apoptosis independently during Drosophila development but intersect in the context of DNA damage. PLoS Genet. 2008;4:e1000153 pubmed publisher
  3. Royzman I, Whittaker A, Orr Weaver T. Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program. Genes Dev. 1997;11:1999-2011 pubmed
    ..Both dDP and dE2F are necessary for viability, and mutations in the genes cause lethality at the late larval/pupal stage. The mutant phenotypes reveal that both genes promote progression of the cell cycle. ..
  4. Frolov M, Huen D, Stevaux O, Dimova D, Balczarek Strang K, Elsdon M, et al. Functional antagonism between E2F family members. Genes Dev. 2001;15:2146-60 pubmed
    ..This study shows how repressor and activator E2Fs are used to pattern transcription and how the net effect of E2F on cell proliferation results from the interplay between two types of E2F complexes that have antagonistic functions. ..
  5. Zraly C, Marenda D, Dingwall A. SNR1 (INI1/SNF5) mediates important cell growth functions of the Drosophila Brahma (SWI/SNF) chromatin remodeling complex. Genetics. 2004;168:199-214 pubmed
    ..Thus, in addition to important functions of the Brm complex in G1-S control, the complex also appears to be important for transcription of genes required for cell cycle progression. ..
  6. Swanhart L, Sanders A, Duronio R. Normal regulation of Rbf1/E2f1 target genes in Drosophila type 1 protein phosphatase mutants. Dev Dyn. 2007;236:2567-77 pubmed
    ..We conclude that PP1 is not a major regulator of the Rbf1/E2F1 pathway in Drosophila. ..
  7. Follette P, Duronio R, O Farrell P. Fluctuations in cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila. Curr Biol. 1998;8:235-8 pubmed
    ..These results indicate that endocycle S phases require oscillations in Cdk activity, but, in contrast to oscillations in mitotic cells, these occur independently of mitosis. ..
  8. Sauer K, Knoblich J, Richardson H, Lehner C. Distinct modes of cyclin E/cdc2c kinase regulation and S-phase control in mitotic and endoreduplication cycles of Drosophila embryogenesis. Genes Dev. 1995;9:1327-39 pubmed
    ..Observations in cyclin A mutants implicate G2 cyclins in this regulation. Our results suggest molecular explanations for the different rules governing S phase during mitotic and endoreduplication cycles. ..
  9. Chen X, Oh S, Zheng Z, Chen H, Shin H, Hou S. Cyclin D-Cdk4 and cyclin E-Cdk2 regulate the Jak/STAT signal transduction pathway in Drosophila. Dev Cell. 2003;4:179-90 pubmed
    ..STAT92E regulates gene expression for various biological processes, including the endocycle S phase. These data suggest that Cyclin D-Cdk4 and Cyclin E-Cdk2 play more versatile roles in Drosophila development. ..
  10. Fuss B, Meissner T, Bauer R, Lehmann C, Eckardt F, Hoch M. Control of endoreduplication domains in the Drosophila gut by the knirps and knirps-related genes. Mech Dev. 2001;100:15-23 pubmed
    ..Our results provide a novel link between morphogen-dependent positional information and the spatio-temporal regulation of cell cycle activity in the gut. ..
  11. Ashburner M, Ball C, Blake J, Botstein D, Butler H, Cherry J, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25:25-9 pubmed
  12. Asano M, Wharton R. E2F mediates developmental and cell cycle regulation of ORC1 in Drosophila. EMBO J. 1999;18:2435-48 pubmed
    ..Furthermore, we find that overexpression of ORC1 alters the pattern of DNA synthesis in the eye disc and the ovary. Thus, replication origin activity appears to be governed in part by the level of ORC1 in Drosophila. ..
  13. Duronio R, Bonnette P, O Farrell P. Mutations of the Drosophila dDP, dE2F, and cyclin E genes reveal distinct roles for the E2F-DP transcription factor and cyclin E during the G1-S transition. Mol Cell Biol. 1998;18:141-51 pubmed
    ..As expected for a defect in the dE2F partner, this mutation blocks G1-S transcription of DmRNR2 and cyclin E as previously described for mutations of dE2F...
  14. Royzman I, Orr Weaver T. S phase and differential DNA replication during Drosophila oogenesis. Genes Cells. 1998;3:767-76 pubmed
    ..Cyclin E and E2F are needed for this differential DNA replication during Drosophila oogenesis. ..
  15. Davidson J, Duronio R. S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues. PLoS Genet. 2012;8:e1002831 pubmed publisher
    ..We propose that inappropriate accumulation of E2f1 protein during S phase triggers the elimination of potentially hyperplastic cells via apoptosis in order to ensure normal development of rapidly proliferating tissues. ..
  16. Maqbool S, Mehrotra S, Kolpakas A, Durden C, Zhang B, Zhong H, et al. Dampened activity of E2F1-DP and Myb-MuvB transcription factors in Drosophila endocycling cells. J Cell Sci. 2010;123:4095-106 pubmed publisher
    ..Our data suggest that dampened transcriptional activation by E2F1-DP and Myb-MuvB is important to repress mitosis and coordinate the endocycle transcriptional and protein stability oscillators. ..
  17. King E, Kislukhin G, Walters K, Long A. Using Drosophila melanogaster to identify chemotherapy toxicity genes. Genetics. 2014;198:31-43 pubmed publisher
    ..We find little evidence for nonsynonymous SNPs explaining mapped QTL; thus it seems likely that standing variation in toxicity is due to regulatory alleles. ..
  18. Meyer C, Jacobs H, Lehner C. Cyclin D-cdk4 is not a master regulator of cell multiplication in Drosophila embryos. Curr Biol. 2002;12:661-6 pubmed
    ..on Cyclin E expression and does not interfere with the initial G1 arrest, while it readily induces the E2F target RnrS in arresting epidermal cells...
  19. Emmerich J, Meyer C, de la Cruz A, Edgar B, Lehner C. Cyclin D does not provide essential Cdk4-independent functions in Drosophila. Genetics. 2004;168:867-75 pubmed
    ..The reduced cellular and organismal growth rates observed in both mutants indicate that Cyclin D-Cdk4 acts as a growth driver. ..
  20. Korenjak M, Taylor Harding B, Binné U, Satterlee J, Stevaux O, Aasland R, et al. Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes. Cell. 2004;119:181-93 pubmed
    ..These results reveal an extensive evolutionary conservation of specific pRb repressor complexes that physically combine subunits with established roles in the regulation of transcription, DNA replication, and chromatin structure. ..
  21. Delanoue R, Legent K, Godefroy N, Flagiello D, Dutriaux A, Vaudin P, et al. The Drosophila wing differentiation factor vestigial-scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc. Cell Death Differ. 2004;11:110-22 pubmed
    ..In Drosophila, ectopic vg induces expression of dE2F1 and its targets dRNR2 and string. In addition vg, but not dE2F1, interacts with and induces expression of dihydrofolate reductase (DHFR)...
  22. Zielke N, Querings S, Rottig C, Lehner C, Sprenger F. The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles. Genes Dev. 2008;22:1690-703 pubmed publisher
    ..Geminin is only abundant in cells with high CycE-Cdk2 activity, suggesting that APC/C-Fzr activity is periodically inhibited by CycE-Cdk2, to prevent relicensing in S-phase cells. ..
  23. Cayirlioglu P, Bonnette P, Dickson M, Duronio R. Drosophila E2f2 promotes the conversion from genomic DNA replication to gene amplification in ovarian follicle cells. Development. 2001;128:5085-98 pubmed
    ..These data indicate that E2f2 functions to inhibit widespread genomic DNA synthesis in late stage follicle cells, and may do so by repressing the expression of specific components of the replication machinery. ..
  24. Hsieh T, Nicolay B, Frolov M, Moon N. Tuberous sclerosis complex 1 regulates dE2F1 expression during development and cooperates with RBF1 to control proliferation and survival. PLoS Genet. 2010;6:e1001071 pubmed publisher
    ..Our results provide evidence to suggest that dE2F1 is an important cell cycle regulator that translates the growth-promoting signal downstream of the TSC/Rheb/Tor/S6k pathway. ..
  25. Myster D, Bonnette P, Duronio R. A role for the DP subunit of the E2F transcription factor in axis determination during Drosophila oogenesis. Development. 2000;127:3249-61 pubmed
    ..Thus we have uncovered new functions for E2F transcription factors during development, including an unexpected role in pattern formation. ..
  26. Duronio R, O Farrell P. Developmental control of a G1-S transcriptional program in Drosophila. Development. 1994;120:1503-15 pubmed
    ..defined a coordinate program of transcription of S-phase genes (DNA polymerase alpha, PCNA and the two ribonucleotide reductase subunits) that can be induced by the G1 cyclin, cyclin E...
  27. Bosco G, Du W, Orr Weaver T. DNA replication control through interaction of E2F-RB and the origin recognition complex. Nat Cell Biol. 2001;3:289-95 pubmed
    ..Our results indicate that dE2F1 and Rbf function together at replication origins to limit DNA replication through interactions with DmORC. ..
  28. Johnston L, Edgar B. Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing. Nature. 1998;394:82-4 pubmed
    ..Notch activity creates a third domain by preventing arrest at G2 in wg-expressing cells, resulting in their arrest in G1. ..
  29. Bradley Gill M, Kim M, Feingold D, Yergeau C, Houde J, Moon N. Alternate transcripts of the Drosophila "activator" E2F are necessary for maintenance of cell cycle exit during development. Dev Biol. 2016;411:195-206 pubmed publisher
    ..Overall, our study suggests that specific alternate transcripts of "activator" E2F, dE2F1, may have a dual function on cell cycle progression and cannot simply be viewed as a pro-proliferative transcription factor. ..