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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hcc-1 is a novel nuclear protein containing the SAF-box DNA-binding domain. It binds to both double-stranded and single-stranded DNA with higher affinity for the single-stranded form. In addition, it also binds specifically to scaffold/matrix attachment region DNA. These nucleic acid-binding characteristics suggest a potential function for Hcc-1 as a component of the heterogeneous ribonucleoprotein complex. Using a yeast two-hybrid screen, two DEAD-box RNA helicases, BAT1 and DDX39, were identified as proteins that interact with Hcc-1. Interactions with these RNA helicases suggested a role for Hcc-1 in nucleic acid biogenesis. Expression of Hcc-1 in the HEK293 cell line resulted in a slower growth rate compared to controls (p = 0.0173) and an accumulation of cells at the G2/M phase (p = 0.0276 compared to control HEK293 cells). Taken together, these results suggest a role for Hcc-1 in growth regulation and nucleic acids metabolism.
Cell Mol Life Sci 2004 Sep
PMID:Hcc-1 is a novel component of the nuclear matrix with growth inhibitory function. 1592 60

Escherichia coli contains at least five ATP-dependent DEAD-box RNA helicases which may play important roles in macromolecular metabolism, especially in translation and mRNA decay. Here we demonstrate that one member of this family, CsdA, whose expression is induced by cold shock, interacts physically and functionally with RNase E. Three independent approaches show that after a shift of cultures to 15 degrees C, CsdA co-purifies with RNase E and other components of the RNA degradosome. Moreover, functional assays using reconstituted minimal degradosomes prepared from purified components in vitro show that CsdA can fully replace the resident RNA helicase of the RNA degradosome, RhlB. In addition, under these conditions, CsdA displays RNA-dependent ATPase activity. Taken together, our data are consistent with a model in which CsdA accumulates during the early stages of cold acclimatization and subsequently assembles into degradosomes with RNase E synthesized in cold-adapted cultures. These findings show that the RNA degradosome is a flexible macromolecular machine capable of adapting to altered environmental conditions.
Mol Microbiol 2004 Dec
PMID:Physical and functional interactions among RNase E, polynucleotide phosphorylase and the cold-shock protein, CsdA: evidence for a 'cold shock degradosome'. 1555 78

The non-catalytic region of Escherichia coli RNase E contains a protein scaffold that binds to the other components of the RNA degradosome. Alanine scanning yielded a mutation, R730A, that disrupts the interaction between RNase E and the DEAD-box RNA helicase, RhlB. We show that three other DEAD-box helicases, SrmB, RhlE and CsdA also bind to RNase E in vitro. Their binding differs from that of RhlB because it is not affected by the R730A mutation. Furthermore, the deletion of residues 791-843, which does not affect RhlB binding, disrupts the binding of SrmB, RhlE and CsdA. Therefore, RNase E has at least two RNA helicase binding sites. Reconstitution of a complex containing the protein scaffold of RNase E, PNPase and RhlE shows that RhlE can furnish an ATP-dependent activity that facilitates the degradation of structured RNA by PNPase. Thus, RhlE can replace the function of RhlB in vitro. The results in the accompanying article show that CsdA can also replace RhlB in vitro. Thus, RhlB, RhlE and CsdA are interchangeable in in vitro RNA degradation assays.
Mol Microbiol 2004 Dec
PMID:The RNase E of Escherichia coli has at least two binding sites for DEAD-box RNA helicases: functional replacement of RhlB by RhlE. 1555 79

Nuclear export of mRNA in eukaryotic cells is mediated by soluble transport factors and components of the nuclear pore complex (NPC). The cytoplasmically oriented nuclear pore protein Nup159 plays a critical role in mRNA export through its conserved N-terminal domain (NTD). Here, we report the crystal structure of the Nup159 NTD, refined to 2.5 A. The structure reveals an unusually asymmetric seven-bladed beta-propeller that is structurally conserved throughout eukarya. Using structure-based conservation analysis, we have targeted specific surface residues for mutagenesis. Residue substitutions in a conserved loop of the NTD abolish in vitro binding to Dbp5, a DEAD box helicase required for mRNA export. In vivo, these mutations cause Dbp5 mislocalization and block mRNA export. These findings suggest that the Nup159 NTD functions in mRNA export as a binding platform, tethering shuttling Dbp5 molecules at the nuclear periphery and locally concentrating this mRNA remodeling factor at the cytoplasmic face of the NPC.
Mol Cell 2004 Dec 03
PMID:The N-terminal domain of Nup159 forms a beta-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore. 1557 30

Among genes conserved from bacteria to mammals are those involved in replicating and repairing DNA. Following the complete sequencing of four hemiascomycetous yeast species during the course of the Genolevures 2 project, we have studied the conservation of 106 genes involved in replication, repair, and recombination in Candida glabrata, Kluyveromyces lactis, Debaryomyces hansenii, and Yarrowia lipolytica and compared them with their Saccharomyces cerevisiae orthologues. We found that proteins belonging to the replication fork and to the nucleotide excision repair pathway were-on the average-more conserved than proteins involved in the checkpoint response to DNA damage or in meiotic recombination. The meiotic recombination proteins Spo11p and Mre11p-Rad50p, involved in making meiotic double-strand breaks (DSBs), are conserved as is Mus81p, involved in resolving meiotic recombination intermediates. Interestingly, genes found in organisms in which DSB-repair is required for proper synapsis during meiosis are also found in C. glabrata, K. lactis, and D. hansenii but not in Y. lipolytica, suggesting that two modes of meiotic recombination have been selected during evolution of the hemiascomycetous yeasts. In addition, we found that SGS1 and TOP1, respectively, a DEAD/DEAH helicase and a type I topoisomerase, are duplicated in C. glabrata and that SRS2, a helicase involved in homologous recombination, is tandemly duplicated in K. lactis. Phylogenetic analyses show that the duplicated SGS1 gene evolved faster than the original gene, probably leading to a specialization of function of the duplicated copy.
Mol Biol Evol 2005 Apr
PMID:Comparative genomics of hemiascomycete yeasts: genes involved in DNA replication, repair, and recombination. 1564 19

Structural analysis of nuclear receptor subfamily V orphan nuclear receptors suggests that ligand-independent mechanisms must regulate this subclass of receptors. Here, we report that steroidogenic factor 1 (SF-1) and liver receptor homolog 1 are repressed via posttranslational SUMO modification at conserved lysines within the hinge domain. Indeed, mutating these lysines or adding the SUMO isopeptidase SENP1 dramatically increased both native and Gal4-chimera receptor activities. The mechanism by which SUMO conjugation attenuates SF-1 activity was found to be largely histone deacetylase independent and was unaffected by the AF2 corepressor Dax1. Instead, our data suggest that SUMO-mediated repression involves direct interaction of the DEAD-box protein DP103 with sumoylated SF-1. Of potential E3-SUMO ligase candidates, PIASy and PIASxalpha strongly promoted SF-1 sumoylation, and addition of DP103 enhanced both PIAS-dependent receptor sumoylation and SF-1 relocalization to discrete nuclear bodies. Taken together, we propose that DEAD-box RNA helicases are directly coupled to transcriptional repression by protein sumoylation.
Mol Cell Biol 2005 Mar
PMID:The DEAD-box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification. 1571 42

The fundamental biology and the biochemical processes at different developmental stages of the malaria parasite Plasmodium falciparum have not been explored in detail. As a step toward understanding the various mechanisms engaged in nucleic acid metabolism of this pathogen, particularly the essential enzymes involved in nucleic acid unwinding, recently, we have reported the isolation of the first P. falciparum DEAD-box DNA helicase 60 (PfDH60), which contained striking homology with p68 protein [Pradhan A, Chauhan VS, Tuteja R. A novel 'DEAD-box' DNA helicase from Plasmodium falciparum is homologous to p68. Mol Biochem Parasitol 2005;140:55-60]. In this study, we show novel important properties of PfDH60. Immunofluorescence assay studies revealed that the peak expression of PfDH60 is mainly in the schizont stages of the development of P. falciparum, where DNA replication is active. Interestingly, this is a bipolar DNA helicase, which unwinds dsDNA in both the directions. PfDH60 can also unwind RNA-DNA and RNA-RNA duplexes. PfDH60 is phosphorylated by protein kinase C at the Ser and Thr residues. The helicase and ATPase activities of PfDH60 were stimulated after this phosphorylation. The cell-cycle dependent expression, bipolar translocation and dual nature collectively suggest that PfDH60 may be involved in the process of DNA replication and distinct cellular processes in the parasite and this study should make an important contribution in our better understanding of DNA metabolic pathways such as repair, recombination and replication.
Mol Biochem Parasitol 2005 Dec
PMID:Plasmodium falciparum DNA helicase 60 is a schizont stage specific, bipolar and dual helicase stimulated by PKC phosphorylation. 1616 32

Around 70 yeast snoRNAs guide rRNA modification, frequently forming base-paired interactions predicted to be very stable at physiological temperatures. Eighteen putative RNA helicases are required for ribosome synthesis, but their actual substrates were not known. We report that depletion of the DEAD box helicase Dbp4p dramatically increased cosedimentation of the snoRNAs U14 and snR41 with preribosomes. Cosedimentation was maintained after deproteinization by proteinase K, indicating that the snoRNAs remained base paired to the pre-rRNA. Affinity purification showed that U14 was strongly accumulated in early 90S preribosomes and depleted from later pre-40S complexes. U14 is required for pre-rRNA processing, and depletion of Dbp4p caused a very similar pre-rRNA processing defect, perhaps due to the reduced pool of free U14. Point mutations in helicase motifs I and III of Dbp4p blocked release of U14 from preribosomes. We conclude that the helicase activity of Dbp4p is required to unwind U14 and snR41 from the pre-rRNA.
Mol Cell 2005 Oct 07
PMID:The Putative RNA Helicase Dbp4p Is Required for Release of the U14 snoRNA from Preribosomes in Saccharomyces cerevisiae. 1620 45

Eukaryotic mRNAs are exported from the nucleus to the cytoplasm as complex mRNA-protein particles (mRNPs), and translocation through the nuclear pore complex (NPC) is accompanied by extensive structural changes of the mRNP. We have tested the hypothesis that the DEAD-box ATPase Dbp5p is required for such an mRNP rearrangement. In dbp5 mutant cells, the mRNA export receptor Mex67p accumulates on mRNA. This aberrant accumulation of Mex67p with RNA and the cold-sensitive growth phenotype of a dbp5 allele are suppressed by a mex67 mutation. Moreover, Mex67 bound mRNA accumulates at the nuclear rim in a temperature-sensitive dbp5 mutant when the nuclear exosome is impaired. Importantly, although accumulation of Mex67p-containing mRNPs is also observed when a nuclear basket component is mutated, these mRNPs still contain the nuclear export factor Yra1p. In contrast, the dbp5-trapped mRNPs lack Yra1p. We propose that Dbp5p's function is specifically required to displace Mex67p from exported mRNPs, thus terminating export.
Mol Cell 2005 Nov 23
PMID:The DEAD-box protein Dbp5p is required to dissociate Mex67p from exported mRNPs at the nuclear rim. 1630 27

In this paper we present soluble dendritic polyglycerol (PG) supported reagents PG-DEAD, PG-PPh3, and PG-DCC as well as scavengers PG-carbonate, PG-carbazate, and PG-amine, which all have been synthesized in high overall conversions and yields using simple purification techniques. The supported reagents have been used simultaneously in Mitsunobu and acylation reactions. All polymeric reagents and scavengers can be removed by simple precipitation/filtration protocols to give chromatography-free products of high purity. In the course of the syntheses of the polymeric reagents three intermediates turned out to be precious polyglycerol derivatives: a mixed carbonate as an electrophilic derivative, polyglyceryl carbazate as a scavenger for carbonyl compounds, as well as polyglycerylamines as amino analogues of polyglycerol.
Mol Divers 2005
PMID:High-loading polyglycerol supported reagents for Mitsunobu- and acylation-reactions and other useful polyglycerol derivatives. 1631 7


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