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

• Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2 [6].

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

• Functions of yeast helicase Ssl2p that are essential for viability are also involved in protection from the toxicity of adriamycin [12].

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

• The INO80 complex contains about 12 polypeptides including two proteins related to the bacterial RuvB DNA helicase, which catalyses branch migration of Holliday junctions [28].
• A human protein with homology to Saccharomyces cerevisiae SNF5 interacts with the potential helicase hbrm [29].
• Both STH1 and SNF2 contain a putative nucleoside triphosphate-binding site and sequences resembling the consensus helicase motifs [30].
• The first new PCNA-binding protein identified in this manner is the 5' to 3' DNA helicase RRM3 [31].
• We report here that Mcm10 binding to replication origins in budding yeast is cell cycle regulated and dependent on the putative helicase, Mcm2-7 [32].

Regulatory relationships of ECM32

• The Saccharomyces cerevisiae DNA2 gene encodes a DNA-stimulated ATPase and DNA helicase/nuclease essential for DNA replication [33].
• The hyper-gene conversion srs2-101 mutation of the SRS2 DNA helicase gene of Saccharomyces cerevisiae has been reported to suppress the UV sensitivity of rad18 mutants [34].
• That the rad3 Arg-48 mutation inactivates the DNA and DNA.RNA helicase activities and confers a substantial reduction in the incision of UV-damaged DNA suggests a role for these activities in incision [35].
• Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity [36].
• The DNA helicase has a 5' to 3' directionality and is only marginally stimulated by coating the single-stranded DNA with the yeast single-stranded DNA-binding protein RF-A [37].

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

• An 'electronic' gene mapping procedure based on computer-aided search for overlapping gene sequences was used to identify adjacent genes and localize several putative RNA helicase genes to different chromosomes [42].
• Here we show, by both 2D gel analyses and chromatin immunoprecipitations (ChIP), that there exists a second level of global control mediated by the intra-S-phase checkpoint protein complex of Tof1p and Csm3p that protect stalled forks at Ter sites against the activity of the Rrm3p helicase ("sweepase") [43].
• The molecular cloning of the gene encoding the Escherichia coli 75-kDa helicase and the determination of its nucleotide sequence and gentic map position [44].
• This DNA helicase co-purified with replication factor C (RF-C) during chromatography on S-Sepharose, DEAE-silica gel high performance liquid chromatography (HPLC), Affi-Gel Blue-agarose, heparin-agarose, single-stranded DNA-cellulose, fast protein liquid chromatography MonoS, and hydroxyapatite HPLC [37].
• Interaction of DnaI with the DnaC helicase by the yeast two-hybrid assay suggests that DnaI acts as a helicase loader [45].

References