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991.
992.
The major mission of the cell division cycle is a faithful and complete duplication of the genome followed by an equal partitioning of chromosomes to subsequent cell generations. In this review, we discuss the advances in our understanding of how mammalian cells control the fidelity of these fundamental processes when exposed to diverse genotoxic insults. We focus on the most recent insights into the molecular pathways that link the sites of DNA lesions with the cell cycle machinery in specific phases of the cell cycle. We also highlight the potential of a new technology allowing direct visualization of molecular interactions and redistribution of checkpoint proteins in live cell nuclei, and document the emerging significance of live-cell imaging for elucidation of the spatio-temporal organization of the DNA damage response network. 相似文献
993.
Weibel P Hiltbrunner A Brand L Kessler F 《The Journal of biological chemistry》2003,278(39):37321-37329
Import of chloroplast precursor proteins is controlled by the coordinate action of two homologous GTPases, Toc159 and Toc33, located at the cytosol-outer membrane interface. Recent studies in Arabidopsis showed that the cytosolic form of the precursor binding protein Toc159 is targeted to its receptor at the import machinery, Toc33, via heterodimerization of their GTP-binding domains. Toc33 may also form GDP-bound homodimers, as suggested by the crystal structure of its pea ortholog. Moreover, the structural data suggested that arginine 130 (Arg130) of Arabidopsis Toc33 may function as a GTPase-activating "arginine-finger" at the other monomer in the Toc33 dimer. Here, we demonstrate that Arg130 of Toc33 does not function as an Arginine-finger. A mutant, Toc33-R130A, binds and hydrolyzes GTP like the wild type. However, we demonstrate that Arg130 is involved in both homodimerization of Toc33 and in heterodimerization with the GTP-binding domain of Toc159. The dependence of Toc33 homodimerization on Arg130 is mutual, requiring the presence of Arg130 at both monomers. As the GTPase is not activated by dimerization, it may be activated independently at either monomer, possibly even before dimerization. Independent regulation of GTPase activity may serve to coordinate the interactions of the GTPases during the import of proteins into the chloroplast. 相似文献
994.
995.
Solution structures of stem-loop RNAs that bind to the two N-terminal RNA-binding domains of nucleolin 下载免费PDF全文
Nucleolin, a multi-domain protein involved in ribosome biogenesis, has been shown to bind the consensus sequence (U/G)CCCG(A/G) in the context of a hairpin loop structure (nucleolin recognition element; NRE). Previous studies have shown that the first two RNA-binding domains in nucleolin (RBD12) are responsible for the interaction with the in vitro selected NRE (sNRE). We have previously reported the structures of nucleolin RBD12, sNRE and nucleolin RBD12–sNRE complex. A comparison of free and bound sNRE shows that the NRE loop becomes structured upon binding. From this observation, we hypothesized that the disordered hairpin loop of sNRE facilitates conformational rearrangements when the protein binds. Here, we show that nucleolin RBD12 is also sufficient for sequence- specific binding of two NRE sequences found in pre-rRNA, b1NRE and b2NRE. Structural investigations of the free NREs using NMR spectroscopy show that the b1NRE loop is conformationally heterogeneous, while the b2NRE loop is structured. The b2NRE forms a hairpin capped by a YNMG-like tetraloop. Comparison of the chemical shifts of sNRE and b2NRE in complex with nucleolin RBD12 suggests that the NRE consensus nucleotides adopt a similar conformation. These results show that a disordered NRE consensus sequence is not a prerequisite for nucleolin RBD12 binding. 相似文献
996.
Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors 总被引:1,自引:0,他引:1
Thullberg M Bartkova J Khan S Hansen K Rönnstrand L Lukas J Strauss M Bartek J 《FEBS letters》2000,470(2):161-166
p16(INK4a), p15(INK4b), p18(INK4c) and p19(INK4d) comprise a family of cyclin-dependent kinase inhibitors and tumor suppressors. We report that the INK4 proteins share the ability to arrest cells in G1, and interact with CDK4 or CDK6 with similar avidity. In contrast, only p18 and particularly p19 are phosphorylated in vivo, and each of the human INK4 proteins shows unique expression patterns dependent on cell and tissue type, and differentiation stage. Thus, the INK4 proteins harbor redundant as well as non-overlapping properties, suggesting distinct regulatory modes, and diverse roles for the individual INK4 family members in cell cycle control, cellular differentiation, and multistep oncogenesis. 相似文献
997.
998.
Papassideri IS Trougakos IP Leonard KR Margaritis LH 《Journal of insect physiology》2007,53(4):370-376
The major sites of energy storage during oogenesis in the Drosophila melanogaster oocyte are the alpha- and beta-yolk spheres. By applying biochemical and transmission electron microscopy (TEM) immunogold techniques we found that the beta-yolk spheres contain mainly polysaccharides, while the three main yolk proteins (YPs) are stored in the alpha-yolk spheres of the developing oocyte. Moreover, by using high-resolution TEM of freeze fractured or cryosectioned follicles, we identified the existence of crystalline structures within the alpha-yolk spheres of the mature oocyte. Our subsequent two-dimensional reconstruction analysis revealed that the unit cell of the crystal is about 113 Angstrom x 113 Angstrom. Assuming that the repeating unit is a cylinder of about 110 Angstrom in length and 25 Angstrom in diameter this cylinder would then have a volume of about 50,000 cubic Angstrom, which corresponds to about 40 kDa of protein. This size fits quite well with the known molecular weight of about 40-45 kDa for each of the three D. melanogaster YPs. Overall, our study identifies for the first time the supramolecular arrangement of the alpha-yolk spheres constituent molecules and provides direct evidence for the "natural" crystallization, and therefore the efficient packaging, of the YPs during oogenesis. 相似文献
999.
Female mate choice influences the maintenance of genetic variation by altering the mating success of males with different genotypes. The evolution of preferences themselves, on the other hand, depends on genetic variation present in the population. Few models have tracked this feedback between a choice gene and its effects on genetic variation, in particular when genes that determine offspring viability and attractiveness have dominance effects. Here we build a population genetic model that allows comparing the evolution of various choice rules in a single framework. We first consider preferences for good genes and show that focused preferences for homozygotes evolve more easily than broad preferences, which allow heterozygous males high mating success too. This occurs despite better maintenance of genetic diversity in the latter scenario, and we discuss why empirical findings of superior mating success of heterozygous males consequently do not immediately lead to a better understanding of the lek paradox. Our results thus suggest that the mechanisms that help maintain genetic diversity also have a flipside of making female choice an inaccurate means of producing the desired kind of offspring. We then consider preferences for heterozygosity per se, and show that these evolve only under very special conditions. Choice for compatible genotypes can evolve but its selective advantage diminishes quickly due to frequency-dependent selection. Finally, we show that our model reproduces earlier results on selfing, when the female choice strategy produces assortative mating. Overall, our model indicates that various forms of heterozygote-favouring (or variable) female choice pose a problem for the theory of sexual ornamentation based on indirect benefits, rather than a solution. 相似文献
1000.
De Alwis DM Dutton RL Scharer J Moo-Young M 《Bioprocess and biosystems engineering》2007,30(2):107-113
Hybridoma 130-8F producing anti-F monoclonal antibodies (MAb) were grown in batch and fed-batch mode with glutamine as the
limiting substrate. The initial concentration of glucose varied between 10 and 25 mM but was not growth limiting. Monoclonal
antibody production was identified as being partially growth associated. Employing the cumulative cell hour concept, external
metabolic flux estimates were calculated during the exponential growth phase for MAb, glucose, amino acids, ammonia and lactate.
Through nutritional profiling using principal component analysis (PCA) followed by partial least squares regression (PLS),
key metabolites were identified and grouped for significant positive, significant negative, low level, and negligible correlation
to MAb production, cellular growth, glucose consumption, and ammonia and lactate production. Significant relationships peculiar
to Hybridoma 130-8F were identified, such as demand for two normally non-essential amino acids (asparagine and aspartic acid),
and the positive correlation between MAb and ammonia production.
Industrial Sponsor: Sanofi Pasteur (formerly Aventis Pasteur), Toronto, Canada. 相似文献