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Gene Review

PCNA  -  Proliferating cell nuclear antigen

Drosophila melanogaster

Synonyms: 53/13, CG9193, Cyclin, DmPCNA, Dmel\CG9193, ...
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Disease relevance of mus209

  • Functional analysis using the reconstituted simian virus 40 in vitro DNA replication system demonstrated that Drosophila PCNA could substitute, albeit with reduced efficiency, for human PCNA in stimulating simian virus 40 DNA synthesis [1].
  • The cellular transcription factor DRTF1/E2F is implicated in the control of early cell cycle progression due to its interaction with important regulators of cellular proliferation, such as pocket proteins (for example, the retinoblastoma tumour suppressor gene product), cyclins and cyclin-dependent kinase subunits [2].
  • We describe two temperature-sensitive lethal alleles (mus209(B1) and mus209(2735)) of the Drosophila PCNA gene that, at temperatures permissive for growth, result in hypersensitivity to DNA-damaging agents, suppression of position-effect variegation, and female sterility in which ovaries are underdeveloped and do not produce eggs [3].
  • Procedures were also developed for purification of unmodified wild-type Drosophila PCNA after induction of expression in Escherichia coli [4].

High impact information on mus209

  • Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing [5].
  • While Drosophila fizzy has previously been shown to be required for cyclin destruction during M phase, fzr is required for cyclin removal during G1 when the embryonic epidermal cell proliferation stops and during G2 preceding salivary gland endoreduplication [6].
  • Loss of fzr causes progression through an extra division cycle in the epidermis and inhibition of endoreduplication in the salivary gland, in addition to failure of cyclin removal [6].
  • A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis [7].
  • Therefore, mitosis and consequently cyclin degradation might be triggered at a time when cyclins have reaccumulated to a critical level [8].

Chemical compound and disease context of mus209


Biological context of mus209


Anatomical context of mus209


Associations of mus209 with chemical compounds


Physical interactions of mus209

  • The Drosophila cyclin-dependent protein kinase complex CycD/Cdk4 has been known to drive cellular growth (accumulation of mass) as well as proliferation (cell cycle progression) [21].
  • During cell cycles 2-7, Cdc2/Cyclin complexes are continuously present and show little fluctuation in abundance, phosphomodification, or activity [22].
  • The N-termini of xPontin and xReptin, which mediate the mitogenic effect were mapped to contain c-Myc interaction domains. c-Myc protein promotes cell cycle progression either by transcriptional activation through the c-Myc/Max complex or by repression of cyclin dependent kinase inhibitors (p21, p15) through c-Myc/Miz-1 interaction [23].
  • Here, we demonstrate that the translational repressor Bruno binds the 3' UTR and inhibits the translation of the mitotic cyclin Cyclin A during prophase of meiosis I [24].

Enzymatic interactions of mus209


Regulatory relationships of mus209

  • Armadillo/Pangolin regulates PCNA and DREF promoter activities [25].
  • Rca1 inhibits APC-Cdh1(Fzr) and is required to prevent cyclin degradation in G2 [26].
  • Furthermore, a mutant form of the mitotic kinase Cdk1 that cannot be inhibited by phosphorylation drove a mitotic cyclin into the nucleus and overcame the delay of mitosis induced by irradiation [27].
  • Here, we address whether these changes in cyclin expression are required for endoreduplication by continuously expressing Cyclin A, B, B3 or E in the salivary glands of Drosophila throughout late embryonic and larval development [28].

Other interactions of mus209


Analytical, diagnostic and therapeutic context of mus209


  1. Drosophila proliferating cell nuclear antigen. Structural and functional homology with its mammalian counterpart. Ng, L., Prelich, G., Anderson, C.W., Stillman, B., Fisher, P.A. J. Biol. Chem. (1990) [Pubmed]
  2. Functional conservation of the cell cycle-regulating transcription factor DRTF1/E2F and its pathway of control in Drosophila melanogaster. Hao, X.F., Alphey, L., Bandara, L.R., Lam, E.W., Glover, D., La Thangue, N.B. J. Cell. Sci. (1995) [Pubmed]
  3. Mutual correction of faulty PCNA subunits in temperature-sensitive lethal mus209 mutants of Drosophila melanogaster. Henderson, D.S., Wiegand, U.K., Norman, D.G., Glover, D.M. Genetics (2000) [Pubmed]
  4. Drosophila replication and repair proteins: proliferating cell nuclear antigen (PCNA). Mozzherin, D.J., McConnell, M., Fisher, P.A. Methods (1999) [Pubmed]
  5. Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing. Reis, T., Edgar, B.A. Cell (2004) [Pubmed]
  6. Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles. Sigrist, S.J., Lehner, C.F. Cell (1997) [Pubmed]
  7. A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. de Nooij, J.C., Letendre, M.A., Hariharan, I.K. Cell (1996) [Pubmed]
  8. Expression and function of Drosophila cyclin A during embryonic cell cycle progression. Lehner, C.F., O'Farrell, P.H. Cell (1989) [Pubmed]
  9. A two-dimensional support for selective binding of polyhistidine-tagged proteins: identification of a proliferating cell nuclear antigen point mutant with altered function in vitro. Zaika, A., Mozzherin, D.J., Tan, C.K., Downey, K.M., Fisher, P.A. Anal. Biochem. (1999) [Pubmed]
  10. Characterization of a second proliferating cell nuclear antigen (PCNA2) from Drosophila melanogaster. Ruike, T., Takeuchi, R., Takata, K., Oshige, M., Kasai, N., Shimanouchi, K., Kanai, Y., Nakamura, R., Sugawara, F., Sakaguchi, K. FEBS J. (2006) [Pubmed]
  11. Identification of plu genes and cis-acting elements of PCNA in the Drosophila genus using conservation of gene order. Renault, A.D., Axton, J.M. Gene (2003) [Pubmed]
  12. Dacapo, a cyclin-dependent kinase inhibitor, stops cell proliferation during Drosophila development. Lane, M.E., Sauer, K., Wallace, K., Jan, Y.N., Lehner, C.F., Vaessin, H. Cell (1996) [Pubmed]
  13. Mutagen sensitivity and suppression of position-effect variegation result from mutations in mus209, the Drosophila gene encoding PCNA. Henderson, D.S., Banga, S.S., Grigliatti, T.A., Boyd, J.B. EMBO J. (1994) [Pubmed]
  14. Site-specific mutagenesis of Drosophila proliferating cell nuclear antigen enhances its effects on calf thymus DNA polymerase delta. Mozzherin, D.J., McConnell, M., Miller, H., Fisher, P.A. BMC Biochem. (2004) [Pubmed]
  15. Drosophila proliferating cell nuclear antigen (cyclin) gene: structure, expression during development, and specific binding of homeodomain proteins to its 5'-flanking region. Yamaguchi, M., Nishida, Y., Moriuchi, T., Hirose, F., Hui, C.C., Suzuki, Y., Matsukage, A. Mol. Cell. Biol. (1990) [Pubmed]
  16. Stem cell division is regulated by the microRNA pathway. Hatfield, S.D., Shcherbata, H.R., Fischer, K.A., Nakahara, K., Carthew, R.W., Ruohola-Baker, H. Nature (2005) [Pubmed]
  17. A CAF-1-PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage. Moggs, J.G., Grandi, P., Quivy, J.P., Jónsson, Z.O., Hübscher, U., Becker, P.B., Almouzni, G. Mol. Cell. Biol. (2000) [Pubmed]
  18. Exit from mitosis in Drosophila syncytial embryos requires proteolysis and cyclin degradation, and is associated with localized dephosphorylation. Su, T.T., Sprenger, F., DiGregorio, P.J., Campbell, S.D., O'Farrell, P.H. Genes Dev. (1998) [Pubmed]
  19. Visualization of replication initiation and elongation in Drosophila. Claycomb, J.M., MacAlpine, D.M., Evans, J.G., Bell, S.P., Orr-Weaver, T.L. J. Cell Biol. (2002) [Pubmed]
  20. Interaction of DNA polymerase delta, proliferating cell nuclear antigen, and synthetic oligonucleotide template-primers. Analysis by polyacrylamide gel electrophoresis-band mobility shift assay. Ng, L., McConnell, M., Tan, C.K., Downey, K.M., Fisher, P.A. J. Biol. Chem. (1993) [Pubmed]
  21. Cyclin D/Cdk4: new insights from Drosophila. Frei, C. Cell Cycle (2004) [Pubmed]
  22. Distinct molecular mechanism regulate cell cycle timing at successive stages of Drosophila embryogenesis. Edgar, B.A., Sprenger, F., Duronio, R.J., Leopold, P., O'Farrell, P.H. Genes Dev. (1994) [Pubmed]
  23. Pontin and Reptin regulate cell proliferation in early Xenopus embryos in collaboration with c-Myc and Miz-1. Etard, C., Gradl, D., Kunz, M., Eilers, M., Wedlich, D. Mech. Dev. (2005) [Pubmed]
  24. Bruno inhibits the expression of mitotic cyclins during the prophase I meiotic arrest of Drosophila oocytes. Sugimura, I., Lilly, M.A. Dev. Cell (2006) [Pubmed]
  25. Armadillo/Pangolin regulates PCNA and DREF promoter activities. Kwon, E., Hayashi, Y., Otsuki, K., Hirose, F., Nishida, Y., Yoo, M.A., Yamaguchi, M. Biochim. Biophys. Acta (2004) [Pubmed]
  26. Rca1 inhibits APC-Cdh1(Fzr) and is required to prevent cyclin degradation in G2. Grosskortenhaus, R., Sprenger, F. Dev. Cell (2002) [Pubmed]
  27. Activating the DNA damage checkpoint in a developmental context. Su, T.T., Walker, J., Stumpff, J. Curr. Biol. (2000) [Pubmed]
  28. Continuous Cyclin E expression inhibits progression through endoreduplication cycles in Drosophila. Weiss, A., Herzig, A., Jacobs, H., Lehner, C.F. Curr. Biol. (1998) [Pubmed]
  29. G1 cyclin-dependent kinases are insufficient to reverse dE2F2-mediated repression. Frolov, M.V., Stevaux, O., Moon, N.S., Dimova, D., Kwon, E.J., Morris, E.J., Dyson, N.J. Genes Dev. (2003) [Pubmed]
  30. Drosophila ATR in Double-Strand Break Repair. Larocque, J.R., Jaklevic, B., Su, T.T., Sekelsky, J. Genetics (2007) [Pubmed]
  31. Essential role of E2F recognition sites in regulation of the proliferating cell nuclear antigen gene promoter during Drosophila development. Yamaguchi, M., Hayashi, Y., Matsukage, A. J. Biol. Chem. (1995) [Pubmed]
  32. Germline genomic instability in PCNA mutants of Drosophila: DNA fingerprinting and microsatellite analysis. López, A., Xamena, N., Marcos, R., Velázquez, A. Mutat. Res. (2005) [Pubmed]
  33. Distribution of PCNA during postblastoderm cell division cycles in the Drosophila melanogaster embryo: effect of a string- mutation. Yamaguchi, M., Nishimoto, Y., Hirose, F., Matsukage, A. Cell Struct. Funct. (1995) [Pubmed]
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