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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

sv  -  shaven

Drosophila melanogaster

Synonyms: CG11049, Cat, D-Pax2, D-pax-2, D-pax2, ...
 
 
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Disease relevance of sv

  • We report here that 17.6 contains three long open reading frames comparable with gag, pol and env genes in retrovirus [1].
  • Better homology existed between another part of the copia open reading frame and a region of the retroviral pol gene recently shown to be distinct from reverse transcriptase and required for the integration of circular DNA forms of the retroviral genome to form proviruses [2].
  • It is an A-family DNA polymerase related to Escherichia coli pol I, human POLQ, and Drosophila Mus308 [3].
  • Surprisingly, other signaling factors such as Neph-1, Pax2, and Wilms' tumor suppressor-1 appear to work within later fly retinal development, providing a surprising link between these two disparate tissues [4].
  • RESULTS: To gain insights into their evolutionary story, a sample of thirteen insect endogenous retroviruses, which represents the largest sample analysed until now, was studied by computer-assisted comparison of the translated products of their gag, pol and env genes, as well as their LTR structural features [5].
 

High impact information on sv

  • In vivo, the majority of TRF1 is complexed with BRF and these two proteins colocalize at many polytene chromosome sites containing RNA pol III genes [6].
  • The C4 point mutation of the Drosophila pol II largest subunit confers on the enzyme a lower elongation rate [7].
  • The kinetics of recruitment following transcription initiation suggest that the association is with newly transcribed pol II transcripts [8].
  • Later, biochemical fractionation led to the co-purification of the multi-subunit Mediator complex and RNA polymerase II (pol II) [9].
  • Its three open reading frames encode predicted products resembling the products of the gag, pol and env genes of retroviruses [10].
 

Biological context of sv

  • The ectopic cell death evident in D-Pax2 mutants appears to arise from the cell fate transformation of cone cells into secondary pigment cells, either autonomously or as a result of defective signalling [11].
  • D-Pax2 eye phenotypes, in contrast, are dramatically altered in a p35 background, because cells that normally differentiate as cone and primary pigment cells are subsequently transformed into secondary pigment cells [11].
  • In addition, we have identified a chimeric element, Uvir, carrying a pol coding sequence only distantly related to sequences thus far found in any telomere arrays [12].
  • Also unlike most pol II promoters, the gypsy promoter, which lacks a TATA motif, was found to have an essential sequence at the transcription initiation site, mutation of which abolishes transcription [13].
  • These experiments provide the first functional evidence that the small subunit of DNA pol gamma stimulates processive DNA synthesis by the human catalytic subunit under physiological salt conditions [14].
 

Anatomical context of sv

  • Studies on expression and function of key developmental control genes suggest that the embryonic vertebrate brain has a tripartite ground plan that consists of a forebrain/midbrain, a hindbrain and an intervening midbrain/hindbrain boundary region, which are characterized by the specific expression of the Otx, Hox and Pax2/5/8 genes, respectively [15].
  • As measured by this assay, neither calf thymus pol delta core enzyme nor PCNA alone bind DNA stably [16].
  • In this communication we identify and initially characterize two antagonistic activities in a Xenopus oocyte extract that can modulate the in vitro transcription of RNA polymerase III (pol III) genes (5 S RNA and tRNA genes) [17].
  • We show by the use of gene fusion constructs that the subgenomic 2 kilobase copia RNA, encoding gag products, is expressed as protein in cultured cells at least ten-fold more efficiently than the full genome length RNA, which additionally contains the pol and int open reading frames [18].
  • During Drosophila embryogenesis, the Pax258 gene is shown to be expressed in the precursor cells of the external sensory organs, thus suggesting a role for Pax258 in the early development of the peripheral nervous system of insects [19].
 

Associations of sv with chemical compounds

  • Results of these studies suggested a model whereby transcription-activator proteins, which bind to specific gene regulatory sequences, recruit both Mediator and pol II as a holoenzyme in a one-step mechanism [9].
  • However, our in vitro transcription study reveals that transcription from the human L1 promoter is highly sensitive to tagetitoxin, a selective inhibitor of RNA polymerase III (pol III), but insensitive to 1 micrograms/ml of alpha-amanitin, indicating that the human L1 promoter is pol III-dependent [20].
  • The Saccharomyces cerevisiae RAD30 gene encodes a novel eukaryotic DNA polymerase, pol eta that is able to replicate across cis-syn cyclobutane pyrimidine dimers both accurately and efficiently [21].
  • We observed new characteristics of Drosophila pol. catalytic subunit as follows: Drosophila pol. catalytic subunit synthesized DNA processively in the presence of both Mn(2+) and Mg(2+) ions, but Mn(2+) inhibited the 3'-5' proofreading activity, thereby decreasing the fidelity of DNA replication by 50% [22].
 

Other interactions of sv

  • Mutational inactivation of otd/Otx2 and unpg/Gbx2 result in the loss or misplacement of the brain-specific expression domains of Pax2/5/8 and Hox genes [15].
  • In both cases Wg exerts its effect, at least in part, by negatively regulating the expression of the Pax2 homolog sparkling (spa) [23].
  • A second gene, D-Pax2, genetically interacts with lozenge [11].
 

Analytical, diagnostic and therapeutic context of sv

  • To elucidate the functional roles of the spacer region, we pursued deletion and site-directed mutagenesis of Drosophila pol gamma [24].
  • A possible role of pol III transcription in mechanisms controlling the expression of full-length mdg1-encoded transcripts in the developing fly, which are apparently relaxed in cell culture, is discussed [25].
  • In a previous study, we tried to purify Drosophila pol. catalytic subunit from embryos through seven column chromatographies and study its biochemical properties [22].

References

  1. Identification of the coding sequence for a reverse transcriptase-like enzyme in a transposable genetic element in Drosophila melanogaster. Saigo, K., Kugimiya, W., Matsuo, Y., Inouye, S., Yoshioka, K., Yuki, S. Nature (1984) [Pubmed]
  2. Complete nucleotide sequence of the Drosophila transposable element copia: homology between copia and retroviral proteins. Mount, S.M., Rubin, G.M. Mol. Cell. Biol. (1985) [Pubmed]
  3. Human DNA polymerase N (POLN) is a low fidelity enzyme capable of error-free bypass of 5S-thymine glycol. Takata, K., Shimizu, T., Iwai, S., Wood, R.D. J. Biol. Chem. (2006) [Pubmed]
  4. The signals that drive kidney development: a view from the fly eye. Cagan, R. Curr. Opin. Nephrol. Hypertens. (2003) [Pubmed]
  5. Evolution and phylogeny of insect endogenous retroviruses. Terzian, C., Pélisson, A., Bucheton, A. BMC Evol. Biol. (2001) [Pubmed]
  6. A TRF1:BRF complex directs Drosophila RNA polymerase III transcription. Takada, S., Lis, J.T., Zhou, S., Tjian, R. Cell (2000) [Pubmed]
  7. A slow RNA polymerase II affects alternative splicing in vivo. de la Mata, M., Alonso, C.R., Kadener, S., Fededa, J.P., Blaustein, M., Pelisch, F., Cramer, P., Bentley, D., Kornblihtt, A.R. Mol. Cell (2003) [Pubmed]
  8. Ribosome components are associated with sites of transcription. Brogna, S., Sato, T.A., Rosbash, M. Mol. Cell (2002) [Pubmed]
  9. Interactions between subunits of Drosophila Mediator and activator proteins. Kim, Y.J., Lis, J.T. Trends Biochem. Sci. (2005) [Pubmed]
  10. Invertebrate retroviruses: ZAM a new candidate in D.melanogaster. Leblanc, P., Desset, S., Dastugue, B., Vaury, C. EMBO J. (1997) [Pubmed]
  11. Mutations in lozenge and D-Pax2 invoke ectopic patterned cell death in the developing Drosophila eye using distinct mechanisms. Siddall, N.A., Behan, K.J., Crew, J.R., Cheung, T.L., Fair, J.A., Batterham, P., Pollock, J.A. Dev. Genes Evol. (2003) [Pubmed]
  12. HeT-A elements in Drosophila virilis: retrotransposon telomeres are conserved across the Drosophila genus. Casacuberta, E., Pardue, M.L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  13. Drosophila retrotransposon promoter includes an essential sequence at the initiation site and requires a downstream sequence for full activity. Jarrell, K.A., Meselson, M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  14. The accessory subunit of Xenopus laevis mitochondrial DNA polymerase gamma increases processivity of the catalytic subunit of human DNA polymerase gamma and is related to class II aminoacyl-tRNA synthetases. Carrodeguas, J.A., Kobayashi, R., Lim, S.E., Copeland, W.C., Bogenhagen, D.F. Mol. Cell. Biol. (1999) [Pubmed]
  15. An urbilaterian origin of the tripartite brain: developmental genetic insights from Drosophila. Hirth, F., Kammermeier, L., Frei, E., Walldorf, U., Noll, M., Reichert, H. Development (2003) [Pubmed]
  16. 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]
  17. The identification of two antagonistic activities in a Xenopus oocyte extract that can modulate the in vitro transcription of RNA polymerase III genes. Giardina, C.A., Wu, C.W. J. Biol. Chem. (1990) [Pubmed]
  18. The retrotransposon copia controls the relative levels of its gene products post-transcriptionally by differential expression from its two major mRNAs. Brierley, C., Flavell, A.J. Nucleic Acids Res. (1990) [Pubmed]
  19. The characterization of novel Pax genes of the sea urchin and Drosophila reveal an ancient evolutionary origin of the Pax2/5/8 subfamily. Czerny, T., Bouchard, M., Kozmik, Z., Busslinger, M. Mech. Dev. (1997) [Pubmed]
  20. RNA polymerase III dependence of the human L1 promoter and possible participation of the RNA polymerase II factor YY1 in the RNA polymerase III transcription system. Kurose, K., Hata, K., Hattori, M., Sakaki, Y. Nucleic Acids Res. (1995) [Pubmed]
  21. Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta. McDonald, J.P., Rapić-Otrin, V., Epstein, J.A., Broughton, B.C., Wang, X., Lehmann, A.R., Wolgemuth, D.J., Woodgate, R. Genomics (1999) [Pubmed]
  22. Subunit protein-affinity isolation of Drosophila DNA polymerase catalytic subunit. Oshige, M., Takeuchi, R., Ruike, T., Ruike, R., Kuroda, K., Sakaguchi, K. Protein Expr. Purif. (2004) [Pubmed]
  23. The dominant mutation Glazed is a gain-of-function allele of wingless that, similar to loss of APC, interferes with normal eye development. Brunner, E., Brunner, D., Fu, W., Hafen, E., Basler, K. Dev. Biol. (1999) [Pubmed]
  24. Mutations in the spacer region of Drosophila mitochondrial DNA polymerase affect DNA binding, processivity, and the balance between Pol and Exo function. Luo, N., Kaguni, L.S. J. Biol. Chem. (2005) [Pubmed]
  25. Complex patterns of transcription of a Drosophila retrotransposon in vivo and in vitro by RNA polymerases II and III. Arkhipova, I.R. Nucleic Acids Res. (1995) [Pubmed]
 
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