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211.
Escherichia coli RecBCD is a heterotrimeric helicase/nuclease that catalyses a complex reaction in which double-strand breaks in DNA are processed for repair by homologous recombination. For some time it has been clear that the RecB subunit possesses a 3' --> 5' DNA helicase activity, which was thought to drive DNA translocation and unwinding in the RecBCD holoenzyme. Here we show that purified RecD protein is also a DNA helicase, but one that possesses a 5' --> 3' polarity. We also show that the RecB and RecD helicases are both active in intact RecBCD, because the enzyme remains capable of processive DNA unwinding when either of these subunits is inactivated by mutation. These findings point to a bipolar translocation model for RecBCD in which the two DNA helicases are complementary, travelling with opposite polarities, but in the same direction, on each strand of the antiparallel DNA duplex. This bipolar motor organization helps to explain various biochemical properties of RecBCD, notably its exceptionally high speed and processivity, and offers a mechanistic insight into aspects of RecBCD function. 相似文献
212.
Haem is essential for living organisms, functioning as a crucial element in the redox-sensitive reaction centre in haemproteins. During the biogenesis of these proteins, the haem cofactor is typically incorporated enzymatically into the haem pockets of the apo-haemprotein as the functionally indispensable prosthetic group. A class of ion channel, the large-conductance calcium-dependent Slo1 BK channels, possesses a conserved haem-binding sequence motif. Here we present electrophysiological and structural evidence showing that haem directly regulates cloned human Slo1 channels and wild-type BK channels in rat brain. Both oxidized and reduced haem binds to the hSlo1 channel protein and profoundly inhibits transmembrane K+ currents by decreasing the frequency of channel opening. This direct regulation of the BK channel identifies a previously unknown role of haem as an acute signalling molecule. 相似文献
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214.
An evolutionary capacitor buffers genotypic variation under normal conditions, thereby promoting the accumulation of hidden polymorphism. But it occasionally fails, thereby revealing this variation phenotypically. The principal example of an evolutionary capacitor is Hsp90, a molecular chaperone that targets an important set of signal transduction proteins. Experiments in Drosophila and Arabidopsis have demonstrated three key properties of Hsp90: (1) it suppresses phenotypic variation under normal conditions and releases this variation when functionally compromised; (2) its function is overwhelmed by environmental stress; and (3) it exerts pleiotropic effects on key developmental processes. But whether these properties necessarily make Hsp90 a significant and unique facilitator of adaptation is unclear. Here we use numerical simulations of complex gene networks, as well as genome-scale expression data from yeast single-gene deletion strains, to present a mechanism that extends the scope of evolutionary capacitance beyond the action of Hsp90 alone. We illustrate that most, and perhaps all, genes reveal phenotypic variation when functionally compromised, and that the availability of loss-of-function mutations accelerates adaptation to a new optimum phenotype. However, this effect does not require the mutations to be conditional on the environment. Thus, there might exist a large class of evolutionary capacitors whose effects on phenotypic variation complement the systemic, environment-induced effects of Hsp90. 相似文献
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216.
Allen M Heinzmann A Noguchi E Abecasis G Broxholme J Ponting CP Bhattacharyya S Tinsley J Zhang Y Holt R Jones EY Lench N Carey A Jones H Dickens NJ Dimon C Nicholls R Baker C Xue L Townsend E Kabesch M Weiland SK Carr D von Mutius E Adcock IM Barnes PJ Lathrop GM Edwards M Moffatt MF Cookson WO 《Nature genetics》2003,35(3):258-263
Asthma is a common disease in children and young adults. Four separate reports have linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32 (refs. 1-4), and two mouse genome screens have linked bronchial hyper-responsiveness to the region homologous to 2q14 (refs. 5,6). We found and replicated association between asthma and the D2S308 microsatellite, 800 kb distal to the IL1 cluster on 2q14. We sequenced the surrounding region and constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium (LD) map. SNP association was limited to the initial exons of a solitary gene of 3.6 kb (DPP10), which extends over 1 Mb of genomic DNA. DPP10 encodes a homolog of dipeptidyl peptidases (DPPs) that cleave terminal dipeptides from cytokines and chemokines, and it presents a potential new target for asthma therapy. 相似文献
217.
Parkhill J Sebaihia M Preston A Murphy LD Thomson N Harris DE Holden MT Churcher CM Bentley SD Mungall KL Cerdeño-Tárraga AM Temple L James K Harris B Quail MA Achtman M Atkin R Baker S Basham D Bason N Cherevach I Chillingworth T Collins M Cronin A Davis P Doggett J Feltwell T Goble A Hamlin N Hauser H Holroyd S Jagels K Leather S Moule S Norberczak H O'Neil S Ormond D Price C Rabbinowitsch E Rutter S Sanders M Saunders D Seeger K Sharp S Simmonds M Skelton J Squares R Squares S Stevens K 《Nature genetics》2003,35(1):32-40
Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica are closely related Gram-negative beta-proteobacteria that colonize the respiratory tracts of mammals. B. pertussis is a strict human pathogen of recent evolutionary origin and is the primary etiologic agent of whooping cough. B. parapertussis can also cause whooping cough, and B. bronchiseptica causes chronic respiratory infections in a wide range of animals. We sequenced the genomes of B. bronchiseptica RB50 (5,338,400 bp; 5,007 predicted genes), B. parapertussis 12822 (4,773,551 bp; 4,404 genes) and B. pertussis Tohama I (4,086,186 bp; 3,816 genes). Our analysis indicates that B. parapertussis and B. pertussis are independent derivatives of B. bronchiseptica-like ancestors. During the evolution of these two host-restricted species there was large-scale gene loss and inactivation; host adaptation seems to be a consequence of loss, not gain, of function, and differences in virulence may be related to loss of regulatory or control functions. 相似文献
218.
Gretarsdottir S Thorleifsson G Reynisdottir ST Manolescu A Jonsdottir S Jonsdottir T Gudmundsdottir T Bjarnadottir SM Einarsson OB Gudjonsdottir HM Hawkins M Gudmundsson G Gudmundsdottir H Andrason H Gudmundsdottir AS Sigurdardottir M Chou TT Nahmias J Goss S Sveinbjörnsdottir S Valdimarsson EM Jakobsson F Agnarsson U Gudnason V Thorgeirsson G Fingerle J Gurney M Gudbjartsson D Frigge ML Kong A Stefansson K Gulcher JR 《Nature genetics》2003,35(2):131-138
We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke. 相似文献
219.
Late Cretaceous sediments from the Western Interior of North America yield exceptionally well preserved fossils that serve as proxies for the rapidly changing climate preceding the Cretaceous/Tertiary boundary (about 67-65 Myr ago). Here we reconstruct the ontogenetic history of a Maastrichtian-age fish, Vorhisia vulpes, by using the carbon, oxygen and strontium isotope ratios of four aragonite otoliths collected from the Fox Hills Formation of South Dakota. Individuals of V. vulpes spawned in brackish water (about 70-80% seawater) and during their first year migrated to open marine waters of the Western Interior Seaway, where they remained for 3 years before returning to the estuary, presumably to spawn and die. The mean delta(18)O from the marine growth phase of V. vulpes yields a seawater temperature of 18 degrees C, which is consistent with leaf physiognomy and general-circulation-model temperature estimates for the Western Interior during the latest Maastrichtian. 相似文献
220.
Genome sequence of Bacillus cereus and comparative analysis with Bacillus anthracis 总被引:10,自引:0,他引:10
Ivanova N Sorokin A Anderson I Galleron N Candelon B Kapatral V Bhattacharyya A Reznik G Mikhailova N Lapidus A Chu L Mazur M Goltsman E Larsen N D'Souza M Walunas T Grechkin Y Pusch G Haselkorn R Fonstein M Ehrlich SD Overbeek R Kyrpides N 《Nature》2003,423(6935):87-91
Bacillus cereus is an opportunistic pathogen causing food poisoning manifested by diarrhoeal or emetic syndromes. It is closely related to the animal and human pathogen Bacillus anthracis and the insect pathogen Bacillus thuringiensis, the former being used as a biological weapon and the latter as a pesticide. B. anthracis and B. thuringiensis are readily distinguished from B. cereus by the presence of plasmid-borne specific toxins (B. anthracis and B. thuringiensis) and capsule (B. anthracis). But phylogenetic studies based on the analysis of chromosomal genes bring controversial results, and it is unclear whether B. cereus, B. anthracis and B. thuringiensis are varieties of the same species or different species. Here we report the sequencing and analysis of the type strain B. cereus ATCC 14579. The complete genome sequence of B. cereus ATCC 14579 together with the gapped genome of B. anthracis A2012 enables us to perform comparative analysis, and hence to identify the genes that are conserved between B. cereus and B. anthracis, and the genes that are unique for each species. We use the former to clarify the phylogeny of the cereus group, and the latter to determine plasmid-independent species-specific markers. 相似文献