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Gene Review

ECM32  -  Ecm32p

Saccharomyces cerevisiae S288c

Synonyms: DNA helicase B, DNA helicase III, Extracellular mutant protein 32, HEL1, Hcs B, ...
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Disease relevance of ECM32

  • One protein identified (Sgs1p) is structurally related to E. coli RecQ protein and contains helicase signature motifs [1].
  • For example, the Saccharomyces cerevisiae RAD26 gene protein and the human transcription-repair coupling factor CSB (Cockayne syndrome 8) are highly homologous to known helicases, yet neither encodes an active helicase [2].
  • Clinically relevant mutations in patients with trichothiodystrophy (TTD) and Fanconi anemia disrupt the Fe-S clusters of XPD and FancJ and thereby abolish helicase activity [3].
  • Brome mosaic virus (BMV), a positive-strand RNA virus in the alphavirus-like superfamily, encodes two RNA replication proteins: 1a, which contains a helicase-like domain and a domain implicated in RNA capping, and 2a, which contains a polymerase-like domain [4].
  • The vaccinia NPH-II RNA helicase, a member of the DEAD/DExH-box protein family, has been shown to be a processive, unidirectional RNA helicase with a step size of about one half turn of a helix [5].

Psychiatry related information on ECM32


High impact information on ECM32

  • This work identifies a nuclear polyadenylation complex containing a known exosome cofactor, the RNA helicase Mtr4p; a poly(A) polymerase, Trf4p; and a zinc knuckle protein, Air2p [7].
  • Synthetic interactions defined a DNA helicase genetic network and predicted a role for SRS2 in processing damaged replication forks but, unlike SGS1, not in rDNA replication, DNA topology or lagging strand synthesis [8].
  • The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA [9].
  • Yeast SRS2 encodes another DNA helicase involved in the maintenance of genome integrity [10].
  • The yeast mitochondrial protein Suv3p is a putative NTP-dependent RNA helicase [11].

Chemical compound and disease context of ECM32


Biological context of ECM32

  • Mutations in the conserved cysteine- and histidine-rich regions and ATPase and helicase motifs of Upf1p separate the ability of Upf1p to complement the respiratory impairment of a Deltaupf1 strain from its ability to act as a multicopy suppressor of mitochondrial splicing deficiency, indicating that distinct pathways express these phenotypes [13].
  • The DNA helicase activity was stimulated by yeast replication protein A, indicating a probable function in DNA replication [14].
  • Haploid hel1 deletion strains were constructed and shown to be viable with growth rates equivalent to those of parental strains [15].
  • In the yeast Saccharomyces cerevisiae, the Upf1 protein (Upf1p), which contains a cysteine- and histidine-rich region and nucleoside triphosphate hydrolysis and helicase motifs, was shown to be a trans-acting factor in this decay pathway [16].
  • Mutations in the conserved helicase motifs of Upf1p that inactivate its mRNA decay function while not allowing suppression of leu2-2 and tyr7-1 nonsense alleles have been identified [17].

Anatomical context of ECM32

  • The MTT1 gene product was shown to interact with translation termination factors and is localized to polysomes [18].
  • Using monkey COS cells and human HeLa cells, we demonstrate that expression of human Upf1 protein harboring an arginine-to-cysteine mutation at residue 844 within the RNA helicase domain acts in a dominant-negative fashion to abrogate the decay of nonsense-containing mRNA that takes place (i) in association with nuclei or (ii) in the cytoplasm [19].
  • This is the first demonstration of physical disassembly of the spliceosome, catalyzed by a complex containing a DExD/H-box RNA helicase and two accessory factors, which might function in targeting the helicase to the correct substrate [20].
  • The N-terminal domain of Nup159 forms a beta-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore [21].
  • PIF1: a DNA helicase in yeast mitochondria [22].

Associations of ECM32 with chemical compounds

  • The enzymatic activity of scHelI copurifies with a polypeptide of 135 kDa as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate [23].
  • Both the helicase and nuclease activities of Dna2Pho were inhibited by substrates with RNA segments at the 5'-end of flap DNA, whereas the nuclease activity of Dna2 from S. cerevisiae was reported to be stimulated by RNA segments in the 5'-tail (Bae, S.-H., and Seo, Y. S. (2000) J. Biol. Chem. 38022-38031) [24].
  • The conserved lysine residue (K436) in the helicase motif Ia in the Upf1p was shown to be critical for ATP binding [25].
  • The complex exhibited DNA-stimulated adenosine triphosphatase (ATPase) activity, but lacked helicase activity [26].
  • The Putative RNA Helicase Dbp4p Is Required for Release of the U14 snoRNA from Preribosomes in Saccharomyces cerevisiae [27].

Physical interactions of ECM32


Regulatory relationships of ECM32


Other interactions of ECM32

  • Nonsense suppression is apparently not due to induction of [PSI+], even though cooverexpression of HSP104 alleviated the nonsense suppression phenotype observed in cells overexpressing MTT1, suggesting a more direct role of Hsp104p in the translation termination process [18].
  • This gene is identical to DNA2, encoding a helicase required for DNA replication [38].
  • Dna2 therefore appears to act in repair or lagging strand synthesis together with Pol alpha and Ctf4, in a role that is optimal with, but does not require, full helicase activity [39].
  • Our current work shows that mutation inactivating Sgs1, the yeast RecQ helicase ortholog, also causes accumulation of stalled replication forks and DSBs at the rDNA RFB [40].
  • Degradation of the deadenylated mRNA required the Rrp4p and Ski7p components of the cytoplasmic exosome complex, as well as the putative RNA helicase Ski2p [41].

Analytical, diagnostic and therapeutic context of ECM32


  1. Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation. Watt, P.M., Louis, E.J., Borts, R.H., Hickson, I.D. Cell (1995) [Pubmed]
  2. The Werner syndrome protein is a DNA helicase. Gray, M.D., Shen, J.C., Kamath-Loeb, A.S., Blank, A., Sopher, B.L., Martin, G.M., Oshima, J., Loeb, L.A. Nat. Genet. (1997) [Pubmed]
  3. The DNA Repair Helicases XPD and FancJ Have Essential Iron-Sulfur Domains. Rudolf, J., Makrantoni, V., Ingledew, W.J., Stark, M.J., White, M.F. Mol. Cell (2006) [Pubmed]
  4. Brome mosaic virus RNA replication protein 1a dramatically increases in vivo stability but not translation of viral genomic RNA3. Janda, M., Ahlquist, P. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Are DEAD-box proteins becoming respectable helicases? Linder, P., Daugeron, M.C. Nat. Struct. Biol. (2000) [Pubmed]
  6. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Moreira, M.C., Klur, S., Watanabe, M., Németh, A.H., Le Ber, I., Moniz, J.C., Tranchant, C., Aubourg, P., Tazir, M., Schöls, L., Pandolfo, M., Schulz, J.B., Pouget, J., Calvas, P., Shizuka-Ikeda, M., Shoji, M., Tanaka, M., Izatt, L., Shaw, C.E., M'Zahem, A., Dunne, E., Bomont, P., Benhassine, T., Bouslam, N., Stevanin, G., Brice, A., Guimarães, J., Mendonça, P., Barbot, C., Coutinho, P., Sequeiros, J., Dürr, A., Warter, J.M., Koenig, M. Nat. Genet. (2004) [Pubmed]
  7. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. LaCava, J., Houseley, J., Saveanu, C., Petfalski, E., Thompson, E., Jacquier, A., Tollervey, D. Cell (2005) [Pubmed]
  8. DNA helicase gene interaction network defined using synthetic lethality analyzed by microarray. Ooi, S.L., Shoemaker, D.D., Boeke, J.D. Nat. Genet. (2003) [Pubmed]
  9. The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA. Ivessa, A.S., Zhou, J.Q., Zakian, V.A. Cell (2000) [Pubmed]
  10. Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases. Gangloff, S., Soustelle, C., Fabre, F. Nat. Genet. (2000) [Pubmed]
  11. The DExH box protein Suv3p is a component of a yeast mitochondrial 3'-to-5' exoribonuclease that suppresses group I intron toxicity. Margossian, S.P., Li, H., Zassenhaus, H.P., Butow, R.A. Cell (1996) [Pubmed]
  12. Functions of yeast helicase Ssl2p that are essential for viability are also involved in protection from the toxicity of adriamycin. Furuchi, T., Takahashi, T., Tanaka, S., Nitta, K., Naganuma, A. Nucleic Acids Res. (2004) [Pubmed]
  13. Overexpression of Upf1p compensates for mitochondrial splicing deficiency independently of its role in mRNA surveillance. de Pinto, B., Lippolis, R., Castaldo, R., Altamura, N. Mol. Microbiol. (2004) [Pubmed]
  14. Biochemical and genetic characterization of a replication protein A dependent DNA helicase from the yeast, Saccharomyces cerevisiae. Biswas, E.E., Chen, P.H., Leszyk, J., Biswas, S.B. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  15. Identification of the gene encoding scHelI, a DNA helicase from Saccharomyces cerevisiae. Bean, D.W., Matson, S.W. Yeast (1997) [Pubmed]
  16. Identification and characterization of mutations in the UPF1 gene that affect nonsense suppression and the formation of the Upf protein complex but not mRNA turnover. Weng, Y., Czaplinski, K., Peltz, S.W. Mol. Cell. Biol. (1996) [Pubmed]
  17. Genetic and biochemical characterization of mutations in the ATPase and helicase regions of the Upf1 protein. Weng, Y., Czaplinski, K., Peltz, S.W. Mol. Cell. Biol. (1996) [Pubmed]
  18. Mtt1 is a Upf1-like helicase that interacts with the translation termination factors and whose overexpression can modulate termination efficiency. Czaplinski, K., Majlesi, N., Banerjee, T., Peltz, S.W. RNA (2000) [Pubmed]
  19. A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsense-containing mRNAs in mammalian cells. Sun, X., Perlick, H.A., Dietz, H.C., Maquat, L.E. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  20. Spliceosome disassembly catalyzed by Prp43 and its associated components Ntr1 and Ntr2. Tsai, R.T., Fu, R.H., Yeh, F.L., Tseng, C.K., Lin, Y.C., Huang, Y.H., Cheng, S.C. Genes Dev. (2005) [Pubmed]
  21. The N-terminal domain of Nup159 forms a beta-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore. Weirich, C.S., Erzberger, J.P., Berger, J.M., Weis, K. Mol. Cell (2004) [Pubmed]
  22. PIF1: a DNA helicase in yeast mitochondria. Lahaye, A., Stahl, H., Thines-Sempoux, D., Foury, F. EMBO J. (1991) [Pubmed]
  23. Purification and characterization of a DNA helicase from Saccharomyces cerevisiae. Bean, D.W., Kallam, W.E., Matson, S.W. J. Biol. Chem. (1993) [Pubmed]
  24. Helicase and nuclease activities of hyperthermophile Pyrococcus horikoshii Dna2 inhibited by substrates with RNA segments at 5'-end. Higashibata, H., Kikuchi, H., Kawarabayasi, Y., Matsui, I. J. Biol. Chem. (2003) [Pubmed]
  25. ATP is a cofactor of the Upf1 protein that modulates its translation termination and RNA binding activities. Weng, Y., Czaplinski, K., Peltz, S.W. RNA (1998) [Pubmed]
  26. Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Côté, J., Quinn, J., Workman, J.L., Peterson, C.L. Science (1994) [Pubmed]
  27. The Putative RNA Helicase Dbp4p Is Required for Release of the U14 snoRNA from Preribosomes in Saccharomyces cerevisiae. Kos, M., Tollervey, D. Mol. Cell (2005) [Pubmed]
  28. A chromatin remodelling complex involved in transcription and DNA processing. Shen, X., Mizuguchi, G., Hamiche, A., Wu, C. Nature (2000) [Pubmed]
  29. A human protein with homology to Saccharomyces cerevisiae SNF5 interacts with the potential helicase hbrm. Muchardt, C., Sardet, C., Bourachot, B., Onufryk, C., Yaniv, M. Nucleic Acids Res. (1995) [Pubmed]
  30. An essential Saccharomyces cerevisiae gene homologous to SNF2 encodes a helicase-related protein in a new family. Laurent, B.C., Yang, X., Carlson, M. Mol. Cell. Biol. (1992) [Pubmed]
  31. Saccharomyces cerevisiae RRM3, a 5' to 3' DNA helicase, physically interacts with proliferating cell nuclear antigen. Schmidt, K.H., Derry, K.L., Kolodner, R.D. J. Biol. Chem. (2002) [Pubmed]
  32. Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Ricke, R.M., Bielinsky, A.K. Mol. Cell (2004) [Pubmed]
  33. The pattern of sensitivity of yeast dna2 mutants to DNA damaging agents suggests a role in DSB and postreplication repair pathways. Budd, M.E., Campbell, J.L. Mutat. Res. (2000) [Pubmed]
  34. Analysis of mitotic and meiotic defects in Saccharomyces cerevisiae SRS2 DNA helicase mutants. Palladino, F., Klein, H.L. Genetics (1992) [Pubmed]
  35. DNA.RNA helicase activity of RAD3 protein of Saccharomyces cerevisiae. Bailly, V., Sung, P., Prakash, L., Prakash, S. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  36. Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity. Lo, Y.C., Paffett, K.S., Amit, O., Clikeman, J.A., Sterk, R., Brenneman, M.A., Nickoloff, J.A. Mol. Cell. Biol. (2006) [Pubmed]
  37. A Saccharomyces cerevisiae DNA helicase associated with replication factor C. Li, X., Yoder, B.L., Burgers, P.M. J. Biol. Chem. (1992) [Pubmed]
  38. Characterization of Saccharomyces cerevisiae dna2 mutants suggests a role for the helicase late in S phase. Fiorentino, D.F., Crabtree, G.R. Mol. Biol. Cell (1997) [Pubmed]
  39. Dna2 mutants reveal interactions with Dna polymerase alpha and Ctf4, a Pol alpha accessory factor, and show that full Dna2 helicase activity is not essential for growth. Formosa, T., Nittis, T. Genetics (1999) [Pubmed]
  40. Evidence that yeast SGS1, DNA2, SRS2, and FOB1 interact to maintain rDNA stability. Weitao, T., Budd, M., Campbell, J.L. Mutat. Res. (2003) [Pubmed]
  41. An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3'-->5' degradation. Mitchell, P., Tollervey, D. Mol. Cell (2003) [Pubmed]
  42. Mapping the putative RNA helicase genes by sequence overlapping. Chang, T.H., Baum, B. Yeast (1992) [Pubmed]
  43. The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae. Mohanty, B.K., Bairwa, N.K., Bastia, D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  44. The molecular cloning of the gene encoding the Escherichia coli 75-kDa helicase and the determination of its nucleotide sequence and gentic map position. Wood, E.R., Matson, S.W. J. Biol. Chem. (1989) [Pubmed]
  45. Subcellular localization of Dna-initiation proteins of Bacillus subtilis: evidence that chromosome replication begins at either edge of the nucleoids. Imai, Y., Ogasawara, N., Ishigo-Oka, D., Kadoya, R., Daito, T., Moriya, S. Mol. Microbiol. (2000) [Pubmed]
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