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61.
Gardner MK Haase J Mythreye K Molk JN Anderson M Joglekar AP O'Toole ET Winey M Salmon ED Odde DJ Bloom K 《The Journal of cell biology》2008,180(1):91-100
In budding yeast, the mitotic spindle is comprised of 32 kinetochore microtubules (kMTs) and ~8 interpolar MTs (ipMTs). Upon anaphase onset, kMTs shorten to the pole, whereas ipMTs increase in length. Overlapping MTs are responsible for the maintenance of spindle integrity during anaphase. To dissect the requirements for anaphase spindle stability, we introduced a conditionally functional dicentric chromosome into yeast. When centromeres from the same sister chromatid attach to opposite poles, anaphase spindle elongation is delayed and a DNA breakage-fusion-bridge cycle ensues that is dependent on DNA repair proteins. We find that cell survival after dicentric chromosome activation requires the MT-binding proteins Kar3p, Bim1p, and Ase1p. In their absence, anaphase spindles are prone to collapse and buckle in the presence of a dicentric chromosome. Our analysis reveals the importance of Bim1p in maintaining a stable ipMT overlap zone by promoting polymerization of ipMTs during anaphase, whereas Kar3p contributes to spindle stability by cross-linking spindle MTs. 相似文献
62.
Mariappan M Gande SL Radhakrishnan K Schmidt B Dierks T von Figura K 《The Journal of biological chemistry》2008,283(17):11556-11564
Formylglycine-generating enzyme (FGE) catalyzes the oxidation of a specific cysteine residue in nascent sulfatase polypeptides to formylglycine (FGly). This FGly is part of the active site of all sulfatases and is required for their catalytic activity. Here we demonstrate that residues 34-68 constitute an N-terminal extension of the FGE catalytic core that is dispensable for in vitro enzymatic activity of FGE but is required for its in vivo activity in the endoplasmic reticulum (ER), i.e. for generation of FGly residues in nascent sulfatases. In addition, this extension is needed for the retention of FGE in the ER. Fusing a KDEL retention signal to the C terminus of FGE is sufficient to mediate retention of an N-terminally truncated FGE but not sufficient to restore its biological activity. Fusion of FGE residues 1-88 to secretory proteins resulted in ER retention of the fusion protein. Moreover, when fused to the paralog of FGE (pFGE), which itself lacks FGly-generating activity, the FGE extension (residues 34-88) of this hybrid construct led to partial restoration of the biological activity of co-expressed N-terminally truncated FGE. Within the FGE N-terminal extension cysteine 52 is critical for the biological activity. We postulate that this N-terminal region of FGE mediates the interaction with an ER component to be identified and that this interaction is required for both the generation of FGly residues in nascent sulfatase polypeptides and for retention of FGE in the ER. 相似文献
63.
Sundaresan NR Anish D Sastry KV Saxena VK Nagarajan K Subramani J Leo MD Shit N Mohan J Saxena M Ahmed KA 《Cell and tissue research》2008,332(3):543-554
In chickens, high levels of dietary zinc cause molting, and the reproductive system undergoes complete remodeling concomitant
to feather replacement. In the present study, the expression profiles of cytokines and chemokines were investigated in the
ovary and oviduct of control hens and of hens induced to molt by zinc feeding. The zinc-induced feed-intake suppression, the
changes in corticosterone levels, the immune cell populations in the reproductive tract, and the apoptosis of reproductive
tissues were analyzed. The expression of mRNAs for interleukin-6 (IL-6), interferon-γ (IFN-γ), the avian ortholog of mammalian
IL-8 (chCXCLi2), and a chicken MIP-1β-like chemokine (chCCLi2) in the ovary and of mRNAs for IL-1β, IL-6, IFN-γ, transforming
growth factor-β2, chCXCLi2, and chCCLi2 in the oviduct were upregulated significantly during zinc-induced molting. A simultaneous
feed-intake reduction was observed with higher expression of cytokines and chemokines. The results of the present investigation
also suggested that the upregulation of corticosterone was closely associated with the increased expression of cytokines and
chemokines. An increase in apoptosis within reproductive tissue during tissue regression was also noted. We had previously
observed the upregulation of these cytokines expression in an earlier study (molting by feed withdrawal). However, the pattern
and the level of expression were different among these two methods. These findings indicate that cytokines might be a common
mediator of tissue regression during molting induced by diverse methods, although the pattern of induction is different. Thus,
a high dose of dietary zinc seems to induce reproductive regression via the upregulation of cytokines and chemokines, the
suppression of feed intake, and the increase in serum corticosterone, resulting finally in the apoptosis of reproductive tissues. 相似文献
64.
Rad50, Mre11, and Xrs2 form a nuclease complex that functions in both nonhomologous end-joining (NHEJ) and recombinational repair of DNA double-strand breaks (DSBs). A search for highly expressed cDNAs that suppress the DNA repair deficiency of rad50 mutants yielded multiple isolates of two genes: EXO1 and TLC1. Overexpression of EXO1 or TLC1 increased the resistance of rad50, mre11, and xrs2 mutants to ionizing radiation and MMS, but did not increase resistance in strains defective in recombination (rad51, rad52, rad54, rad59) or NHEJ only (yku70, sir4). Increased Exo1 or TLC1 RNA did not alter checkpoint responses or restore NHEJ proficiency, but DNA repair defects of yku70 and rad27 (fen) mutants were differentially suppressed by the two genes. Overexpression of Exo1, but not mutant proteins containing substitutions in the conserved nuclease domain, increased recombination and suppressed HO and EcoRI endonuclease-induced killing of rad50 strains. exo1 rad50 mutants lacking both nuclease activities exhibited a high proportion of enlarged, G2-arrested cells and displayed a synergistic decrease in DSB-induced plasmid:chromosome recombination. These results support a model in which the nuclease activity of the Rad50/Mre11/Xrs2 complex is required for recombinational repair, but not NHEJ. We suggest that the 5'-3' exo activity of Exo1 is able to substitute for Rad50/Mre11/Xrs2 in rescission of specific classes of DSB end structures. Gene-specific suppression by TLC1, which encodes the RNA subunit of the yeast telomerase complex, demonstrates that components of telomerase can also impact on DSB repair pathways. 相似文献
65.
The ultrastructural studies have shown three types of motor endings in the macaque intrafusal fibers: 1) unindented axon terminals with smooth or shallowly folded postsynaptic membrane; 2) indented terminals with few postsynaptic folds; and 3) indented terminals with heavily folded postsynaptic membrane. The terminals on bag 1 and chain fibers were generally more indented than those on the bag 2 fibers. Deeply indented terminals with highly folded postsynaptic membranes were noticed on the bag 1 and chain endings in spindles from lumbrical but not the biceps muscle. In the individual intrafusal fibers from the biceps and lumbrical spindles, the degree of indentation did not correlate with the extent of postsynaptic folding (P greater than .01). Endings on bag 1 and chain fibers in the lumbrical spindles showed a positive correlation between indentation of terminals and their distance from the primary sensory endings (P less than .01), whereas the lumbrical bag 2 endings and the biceps intrafusal endings did not (P greater than .01). The shape of the intrafusal motor endings thus is independent of their location but dependent on the type of intrafusal fibers. 相似文献
66.
Parasuraman Aiya Subramani Venkata Ramireddy Narala R Dinakaran Michael Dakshayani Lomada Madhava C Reddy 《Bioinformation》2015,11(5):248-253
Protein prenylation is a posttranslational modification that is indispensable for translocation of membrane GTPases like Ras, Rho,
Ras etc. Proteins of Ras family undergo farnesylation by FTase while Rho family goes through geranylgeranylation by GGTase1.
There is only an infinitesimal difference in signal recognition between FTase and GGTase1. FTase inhibitors mostly end up
selecting the cells with mutated Ras proteins that have acquired affinity towards GGTase1 in cancer microcosms. Therefore, it is of
interest to identify GGTase1 and FTase dual inhibitors using the docking tool AutoDock Vina. Docking data show that curcumin
(from turmeric) has higher binding affinity to GGTase1 than that of established peptidomimetic GGTase1 inhibitors (GGTI) such as
GGTI-297, GGTI-298, CHEMBL525185. Curcumin also interacts with FTase with binding energy comparable to co-crystalized
compound 2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-[1-amino-1-(1-methyl-1h-imidizol-5-yl)-ethyl]-benzonitrile (BNE).
The docked complex was further simulated for 10 ns using molecular dynamics simulation for stability. Thus, the molecular basis
for curcumin binding to GGTase1 and FTase is reported. 相似文献
67.
Summary The influence of glycerol and sodium chloride on the stability of arginase entrapped in reverse micellar system of non-ionic surfactant Triton X - 100/n-hexanol/n-hexane, was studied. Entrapped enzyme shows better stability, further enhanced by the addition of these additives. However, the stability with these additives was found to be much better in reverse micelles. 相似文献
68.
K. S. Karthikeyan H. Polasa K. Sivarama Sastry Gopal Reddy 《Indian journal of microbiology》2008,48(3):397-400
Saccharomyces cerevisiae which cannot utilize lysine as a sole nitrogen source is shown to metabolize a Lysine 3 Cr3+ (1:1) complex synthesized, as a combined nitrogen and carbon source. It induces rapid uptake of lysine and prevents loss
of viability, in contrast with free lysine. That complexation with trivalent chromium has the effect of profoundly influencing
intracellular distribution and metabolism of the liganded amino acid is demonstrated. 相似文献
69.
DNA repair in higher plants 总被引:9,自引:0,他引:9
Edward J. Vonarx Helen L. Mitchell Ramachandran Karthikeyan Ishita Chatterjee Bernard A. Kunz 《Mutation research》1998,400(1-2):187-200
Numerous studies have demonstrated a requirement in plants for repair of DNA damage arising from either intrinsic or extrinsic sources. Investigations also have revealed a capacity for repair types of DNA damage, and conversely, identified mutants apparently defective in such repair. This article provides a concise overview of nuclear DNA repair mechanisms in higher plants, particularly those processes concerned with the repair of UV-induced lesions, and includes surveys of UV-sensitive mutants and genes implicated in DNA repair. 相似文献
70.