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911.
Interactions of phage Mu enhancer and termini that specify the assembly of a topologically unique interwrapped transpososome 总被引:1,自引:0,他引:1
The higher-order DNA-protein complex that carries out the chemical steps of phage Mu transposition is organized by bridging interactions among three DNA sites, the left (L) and right (R) ends of Mu, and an enhancer element (E), mediated by the transposase protein MuA. A subset of the six subunits of MuA associated with their cognate sub-sites at L and R communicate with the enhancer to trigger the stepwise assembly of the functional transpososome. The DNA follows a well-defined path within the transpososome, trapping five supercoil nodes comprising two E-R crossings, one E-L crossing and two L-R crossings. The enhancer is a critical DNA element in specifying the unique interwrapped topology of the three-site LER synapse. In this study, we used multiple strategies to characterize Mu end-enhancer interactions to extend, modify and refine those inferred from earlier analyses. Directed placement of transposase subunits at their cognate sub-sites at L and R, analysis of the protein composition of transpososomes thus obtained, and their characterization using topological methods define the following interactions. R1-E interaction is essential to promote transpososome assembly, R3-E interaction contributes to the native topology of the transpososome, and L1-E and R2-E interactions are not required for assembly. The data on L2-E and L3-E interactions are not unequivocal. If they do occur, either one is sufficient to support the assembly process. Our results are consistent with two R-E and perhaps one L-E, being responsible for the three DNA crossings between the enhancer and the left and right ends of Mu. A 3D representation of the interwrapped complex (IW) obtained by modeling is consistent with these results. The model reveals straightforward geometric and topological relationships between the IW complex and a more relaxed enhancer-independent V-form of the transpososome assembled under altered reaction conditions. 相似文献
912.
913.
SET is a multi-functional protein in proliferating cells. Some of the proposed functions of SET suggest an important nuclear role. However, the nuclear import pathway of SET is also unknown and the function of SET in neurons is unclear. Presently, using cortical neurons, we report that the nuclear import of SET is mediated by an impalpha/impbeta-dependent pathway. Nuclear localization signal, (168)KRSSQTQNKASRKR(181), in SET interacts with impalpha3, which recruits impbeta to form a ternary complex, resulting in efficient transportation of SET into nucleus. By in vitro nuclear import assay based on digitonin-permeabilized neurons, we further demonstrated that the nuclear import of SET relies on Ran GTPase. We provide evidence that this nuclear localization of SET is important in neuronal survival. Under basal conditions, SET is predominately nuclear. However, upon death induced by genotoxic stress, endogenous SET decreases in the nucleus and increases in the cytoplasm. Consistent with a toxic role of SET in the cytoplasm, targeted expression of SET to the cytoplasm exacerbates death compared to wild type SET expression which is protective following DNA damage. Taken together, our results indicate that SET is imported into the nucleus through its association with impalpha3/impbeta, and that localization of SET is important in regulation of neuronal death. 相似文献
914.
Prediction of protein coding regions by the 3-base periodicity analysis of a DNA sequence 总被引:2,自引:0,他引:2
With the exponential growth of genomic sequences, there is an increasing demand to accurately identify protein coding regions (exons) from genomic sequences. Despite many progresses being made in the identification of protein coding regions by computational methods during the last two decades, the performances and efficiencies of the prediction methods still need to be improved. In addition, it is indispensable to develop different prediction methods since combining different methods may greatly improve the prediction accuracy. A new method to predict protein coding regions is developed in this paper based on the fact that most of exon sequences have a 3-base periodicity, while intron sequences do not have this unique feature. The method computes the 3-base periodicity and the background noise of the stepwise DNA segments of the target DNA sequences using nucleotide distributions in the three codon positions of the DNA sequences. Exon and intron sequences can be identified from trends of the ratio of the 3-base periodicity to the background noise in the DNA sequences. Case studies on genes from different organisms show that this method is an effective approach for exon prediction. 相似文献
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918.
Zhao Y Difrancesca D Wang X Zarnegar R Michalopoulos GK Yin XM 《Journal of cellular physiology》2007,213(2):556-563
The death receptor pathway is coupled to the mitochondria apoptosis pathway. However, mitochondrial participation, which is stimulated by Bid but suppressed by Bcl-2/Bcl-x(L), is required in certain cells (Type II), but not in others (Type I). While these differences were originally characterized in the lymphoid cell lines, the typical Type II cells are represented by hepatocytes in vivo. The molecular mechanisms that distinguish Type II from Type I cells and the regulation are not fully understood. Fas can be sequestered by the HGF receptor c-Met and high doses of HGF can promote cell death by freeing Fas from c-Met complex. We thus reasoned that treatment of the Type II cells with high doses of HGF could enhance Fas-mediated apoptosis and spare the mitochondria amplification. Indeed, such treatment led to increased apoptosis in Type II lymphoid cells, which could not be blocked by Bcl-x(L). Moreover, significant hepatocyte apoptosis was induced by this scheme in the absence of Bid with increased dissociation of Fas from c-Met. These findings indicate that high doses of HGF could be used to promote apoptosis in Type II cells bypassing the requirement for mitochondria activation. 相似文献
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920.