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151.
Human CtIP promotes DNA end resection 总被引:3,自引:0,他引:3
Sartori AA Lukas C Coates J Mistrik M Fu S Bartek J Baer R Lukas J Jackson SP 《Nature》2007,450(7169):509-514
In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination. 相似文献
152.
Hessa T Meindl-Beinker NM Bernsel A Kim H Sato Y Lerch-Bader M Nilsson I White SH von Heijne G 《Nature》2007,450(7172):1026-1030
153.
Proteomic studies have yielded detailed lists of the proteins present in a cell. Comparatively little is known, however, about how these proteins interact and are spatially arranged within the 'functional modules' of the cell: that is, the 'molecular sociology' of the cell. This gap is now being bridged by using emerging experimental techniques, such as mass spectrometry of complexes and single-particle cryo-electron microscopy, to complement traditional biochemical and biophysical methods. With the development of integrative computational methods to exploit the data obtained, such hybrid approaches will uncover the molecular architectures, and perhaps even atomic models, of many protein complexes. With these structures in hand, researchers will be poised to use cryo-electron tomography to view protein complexes in action within cells, providing unprecedented insights into protein-interaction networks. 相似文献
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155.
Piccioni G Drossart P Sanchez-Lavega A Hueso R Taylor FW Wilson CF Grassi D Zasova L Moriconi M Adriani A Lebonnois S Coradini A Bézard B Angrilli F Arnold G Baines KH Bellucci G Benkhoff J Bibring JP Blanco A Blecka MI Carlson RW Di Lellis A Encrenaz T Erard S Fonti S Formisano V Fouchet T Garcia R Haus R Helbert J Ignatiev NI Irwin PG Langevin Y Lopez-Valverde MA Luz D Marinangeli L Orofino V Rodin AV Roos-Serote MC Saggin B Stam DM Titov D Visconti G 《Nature》2007,450(7170):637-640
Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition. 相似文献
156.
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158.
Sato T Mushiake S Kato Y Sato K Sato M Takeda N Ozono K Miki K Kubo Y Tsuji A Harada R Harada A 《Nature》2007,448(7151):366-369
A number of proteins are known to be involved in apical/basolateral transport of proteins in polarized epithelial cells. The small GTP-binding protein Rab8 was thought to regulate basolateral transport in polarized kidney epithelial cells through the AP1B-complex-mediated pathway. However, the role of Rab8 (Rab8A) in cell polarity in vivo remains unknown. Here we show that Rab8 is responsible for the localization of apical proteins in intestinal epithelial cells. We found that apical peptidases and transporters localized to lysosomes in the small intestine of Rab8-deficient mice. Their mislocalization and degradation in lysosomes led to a marked reduction in the absorption rate of nutrients in the small intestine, and ultimately to death. Ultrastructurally, a shortening of apical microvilli, an increased number of enlarged lysosomes, and microvillus inclusions in the enterocytes were also observed. One microvillus inclusion disease patient who shows an identical phenotype to Rab8-deficient mice expresses a reduced amount of RAB8 (RAB8A; NM_005370). Our results demonstrate that Rab8 is necessary for the proper localization of apical proteins and the absorption and digestion of various nutrients in the small intestine. 相似文献
159.
160.
Guerlin C Bernu J Deléglise S Sayrin C Gleyzes S Kuhr S Brune M Raimond JM Haroche S 《Nature》2007,448(7156):889-893
The irreversible evolution of a microscopic system under measurement is a central feature of quantum theory. From an initial state generally exhibiting quantum uncertainty in the measured observable, the system is projected into a state in which this observable becomes precisely known. Its value is random, with a probability determined by the initial system's state. The evolution induced by measurement (known as 'state collapse') can be progressive, accumulating the effects of elementary state changes. Here we report the observation of such a step-by-step collapse by non-destructively measuring the photon number of a field stored in a cavity. Atoms behaving as microscopic clocks cross the cavity successively. By measuring the light-induced alterations of the clock rate, information is progressively extracted, until the initially uncertain photon number converges to an integer. The suppression of the photon number spread is demonstrated by correlations between repeated measurements. The procedure illustrates all the postulates of quantum measurement (state collapse, statistical results and repeatability) and should facilitate studies of non-classical fields trapped in cavities. 相似文献