排序方式: 共有57条查询结果,搜索用时 15 毫秒
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A hallmark feature of DNA replication is the coordination between the continuous polymerization of nucleotides on the leading strand and the discontinuous synthesis of DNA on the lagging strand. This synchronization requires a precisely timed series of enzymatic steps that control the synthesis of an RNA primer, the recycling of the lagging-strand DNA polymerase, and the production of an Okazaki fragment. Primases synthesize RNA primers at a rate that is orders of magnitude lower than the rate of DNA synthesis by the DNA polymerases at the fork. Furthermore, the recycling of the lagging-strand DNA polymerase from a finished Okazaki fragment to a new primer is inherently slower than the rate of nucleotide polymerization. Different models have been put forward to explain how these slow enzymatic steps can take place at the lagging strand without losing coordination with the continuous and fast leading-strand synthesis. Nonetheless, a clear picture remains elusive. Here we use single-molecule techniques to study the kinetics of a multiprotein replication complex from bacteriophage T7 and to characterize the effect of primase activity on fork progression. We observe the synthesis of primers on the lagging strand to cause transient pausing of the highly processive leading-strand synthesis. In the presence of both leading- and lagging-strand synthesis, we observe the formation and release of a replication loop on the lagging strand. Before loop formation, the primase acts as a molecular brake and transiently halts progression of the replication fork. This observation suggests a mechanism that prevents leading-strand synthesis from outpacing lagging-strand synthesis during the slow enzymatic steps on the lagging strand. 相似文献
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In 1961, Rolf Landauer argued that the erasure of information is a dissipative process. A minimal quantity of heat, proportional to the thermal energy and called the Landauer bound, is necessarily produced when a classical bit of information is deleted. A direct consequence of this logically irreversible transformation is that the entropy of the environment increases by a finite amount. Despite its fundamental importance for information theory and computer science, the erasure principle has not been verified experimentally so far, the main obstacle being the difficulty of doing single-particle experiments in the low-dissipation regime. Here we experimentally show the existence of the Landauer bound in a generic model of a one-bit memory. Using a system of a single colloidal particle trapped in a modulated double-well potential, we establish that the mean dissipated heat saturates at the Landauer bound in the limit of long erasure cycles. This result demonstrates the intimate link between information theory and thermodynamics. It further highlights the ultimate physical limit of irreversible computation. 相似文献
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LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription 总被引:4,自引:0,他引:4
Metzger E Wissmann M Yin N Müller JM Schneider R Peters AH Günther T Buettner R Schüle R 《Nature》2005,437(7057):436-439
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Blain S Quéguiner B Armand L Belviso S Bombled B Bopp L Bowie A Brunet C Brussaard C Carlotti F Christaki U Corbière A Durand I Ebersbach F Fuda JL Garcia N Gerringa L Griffiths B Guigue C Guillerm C Jacquet S Jeandel C Laan P Lefèvre D Lo Monaco C Malits A Mosseri J Obernosterer I Park YH Picheral M Pondaven P Remenyi T Sandroni V Sarthou G Savoye N Scouarnec L Souhaut M Thuiller D Timmermans K Trull T Uitz J van Beek P Veldhuis M Vincent D Viollier E Vong L Wagener T 《Nature》2007,446(7139):1070-1074
The availability of iron limits primary productivity and the associated uptake of carbon over large areas of the ocean. Iron thus plays an important role in the carbon cycle, and changes in its supply to the surface ocean may have had a significant effect on atmospheric carbon dioxide concentrations over glacial-interglacial cycles. To date, the role of iron in carbon cycling has largely been assessed using short-term iron-addition experiments. It is difficult, however, to reliably assess the magnitude of carbon export to the ocean interior using such methods, and the short observational periods preclude extrapolation of the results to longer timescales. Here we report observations of a phytoplankton bloom induced by natural iron fertilization--an approach that offers the opportunity to overcome some of the limitations of short-term experiments. We found that a large phytoplankton bloom over the Kerguelen plateau in the Southern Ocean was sustained by the supply of iron and major nutrients to surface waters from iron-rich deep water below. The efficiency of fertilization, defined as the ratio of the carbon export to the amount of iron supplied, was at least ten times higher than previous estimates from short-term blooms induced by iron-addition experiments. This result sheds new light on the effect of long-term fertilization by iron and macronutrients on carbon sequestration, suggesting that changes in iron supply from below--as invoked in some palaeoclimatic and future climate change scenarios--may have a more significant effect on atmospheric carbon dioxide concentrations than previously thought. 相似文献
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Yeager M Orr N Hayes RB Jacobs KB Kraft P Wacholder S Minichiello MJ Fearnhead P Yu K Chatterjee N Wang Z Welch R Staats BJ Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cancel-Tassin G Cussenot O Valeri A Andriole GL Gelmann EP Tucker M Gerhard DS Fraumeni JF Hoover R Hunter DJ Chanock SJ Thomas G 《Nature genetics》2007,39(5):645-649
Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%). 相似文献
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Thomas G Jacobs KB Yeager M Kraft P Wacholder S Orr N Yu K Chatterjee N Welch R Hutchinson A Crenshaw A Cancel-Tassin G Staats BJ Wang Z Gonzalez-Bosquet J Fang J Deng X Berndt SI Calle EE Feigelson HS Thun MJ Rodriguez C Albanes D Virtamo J Weinstein S Schumacher FR Giovannucci E Willett WC Cussenot O Valeri A Andriole GL Crawford ED Tucker M Gerhard DS Fraumeni JF Hoover R Hayes RB Hunter DJ Chanock SJ 《Nature genetics》2008,40(3):310-315