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511.
Mechanism of RAD51-dependent DNA interstrand cross-link repair 总被引:2,自引:0,他引:2
DNA interstrand cross-links (ICLs) are toxic DNA lesions whose repair in S phase of eukaryotic cells is incompletely understood. In Xenopus egg extracts, ICL repair is initiated when two replication forks converge on the lesion. Dual incisions then create a DNA double-strand break (DSB) in one sister chromatid, whereas lesion bypass restores the other sister. We report that the broken sister chromatid is repaired via RAD51-dependent strand invasion into the regenerated sister. Recombination acts downstream of FANCI-FANCD2, yet RAD51 binds ICL-stalled replication forks independently of FANCI-FANCD2 and before DSB formation. Our results elucidate the functional link between the Fanconi anemia pathway and the recombination machinery during ICL repair. In addition, they demonstrate the complete repair of a DSB via homologous recombination in vitro. 相似文献
512.
Howlett NG Taniguchi T Olson S Cox B Waisfisz Q De Die-Smulders C Persky N Grompe M Joenje H Pals G Ikeda H Fox EA D'Andrea AD 《Science (New York, N.Y.)》2002,297(5581):606-609
Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA1 or BRCA2 mutations. 相似文献
513.
Mezger M Schröder H Reichert H Schramm S Okasinski JS Schöder S Honkimäki V Deutsch M Ocko BM Ralston J Rohwerder M Stratmann M Dosch H 《Science (New York, N.Y.)》2008,322(5900):424-428
Room-temperature ionic liquids (RTILs) are promising candidates for a broad range of "green" applications, for which their interaction with solid surfaces plays a crucial role. In this high-energy x-ray reflectivity study, the temperature-dependent structures of three ionic liquids with the tris(pentafluoroethyl)trifluorophosphate anion in contact with a charged sapphire substrate were investigated with submolecular resolution. All three RTILs show strong interfacial layering, starting with a cation layer at the substrate and decaying exponentially into the bulk liquid. The observed decay length and layering period point to an interfacial ordering mechanism, akin to the charge inversion effect, which is suggested to originate from strong correlations between the unscreened ions. The observed layering is expected to be a generic feature of RTILs at charged interfaces. 相似文献
514.
Nagel G Ollig D Fuhrmann M Kateriya S Musti AM Bamberg E Hegemann P 《Science (New York, N.Y.)》2002,296(5577):2395-2398
Phototaxis and photophobic responses of green algae are mediated by rhodopsins with microbial-type chromophores. We report a complementary DNA sequence in the green alga Chlamydomonas reinhardtii that encodes a microbial opsin-related protein, which we term Channelopsin-1. The hydrophobic core region of the protein shows homology to the light-activated proton pump bacteriorhodopsin. Expression of Channelopsin-1, or only the hydrophobic core, in Xenopus laevis oocytes in the presence of all-trans retinal produces a light-gated conductance that shows characteristics of a channel selectively permeable for protons. We suggest that Channelrhodopsins are involved in phototaxis of green algae. 相似文献
515.
Salmonella enterica, the cause of food poisoning and typhoid fever, induces actin cytoskeleton rearrangements and membrane ruffling to gain access into nonphagocytic cells, where it can replicate and avoid innate immune defenses. Here, we found that SopB, a phosphoinositide phosphatase that is delivered into host cells by a type III secretion system, was essential for the establishment of Salmonella's intracellular replicative niche. SopB mediated the formation of spacious phagosomes following bacterial entry and was responsible for maintaining high levels of phosphatidylinositol-three-phosphate [PtdIns(3)P] in the membrane of the bacteria-containing vacuoles. Absence of SopB caused a significant defect in the maturation of the Salmonella-containing vacuole and impaired bacterial intracellular growth. 相似文献
516.
517.
Grbin PR Herderich M Markides A Lee TH Henschke PA 《Journal of agricultural and food chemistry》2007,55(26):10872-10879
Mousy off-flavor is an insidious and economically disastrous microbiologically derived spoilage characteristic of wine and other fermented beverages. Tainted wines are rendered unpalatable and there is currently no satisfactory procedure for removal of the off-flavor. Here we report the confirmation of that both d- and l-lysine can act as a precursor for the formation of mousy off-flavor N-heterocycles. Further, through the use of stable isotope feeding experiments, we could establish that a pentylamine group from lysine is incorporated into the piperideine moiety of two off-flavor N-heterocycles. A biochemical pathway for the formation of mousy off-flavor compounds is proposed. 相似文献
518.
Sergey A. Dyshlovoy Larisa K. Shubina Tatyana N. Makarieva Alla G. Guzii Jessica Hauschild Nadja Strewinsky Dmitrii V. Berdyshev Ekaterina K. Kudryashova Alexander S. Menshov Roman S. Popov Pavel S. Dmitrenok Markus Graefen Carsten Bokemeyer Gunhild von Amsberg 《Marine drugs》2022,20(12)
Two new guanidine alkaloids, batzelladines O (1) and P (2), were isolated from the deep-water marine sponge Monanchora pulchra. The structures of these metabolites were determined by NMR spectroscopy, mass spectrometry, and ECD. The isolated compounds exhibited cytotoxic activity in human prostate cancer cells PC3, PC3-DR, and 22Rv1 at low micromolar concentrations and inhibited colony formation and survival of the cancer cells. Batzelladines O (1) and P (2) induced apoptosis, which was detected by Western blotting as caspase-3 and PARP cleavage. Additionally, induction of pro-survival autophagy indicated as upregulation of LC3B-II and suppression of mTOR was observed in the treated cells. In line with this, the combination with autophagy inhibitor 3-methyladenine synergistically increased the cytotoxic activity of batzelladines O (1) and P (2). Both compounds were equally active in docetaxel-sensitive and docetaxel-resistant prostate cancer cells, despite exhibiting a slight p-glycoprotein substrate-like activity. In combination with docetaxel, an additive effect was observed. In conclusion, the isolated new guanidine alkaloids are promising drug candidates for the treatment of taxane-resistant prostate cancer. 相似文献