3,850 research outputs found

    Composition and Dynamics of the Eukaryotic Replisome: A Brief Overview

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    High-fidelity chromosomal DNA replication is vital for maintaining the integrity of the genetic material in all forms of cellular life. In eukaryotic cells, around 40-50 distinct conserved polypeptides are essential for chromosome replication, the majority of which are themselves component parts of a series of elaborate molecular machines that comprise the replication apparatus or replisome. How these complexes are assembled, what structures they adopt, how they perform their functions, and how those functions are regulated, are key questions for understanding how genome duplication occurs. Here I present a brief overview of current knowledge of the dynamic molecular events underlying chromosomal DNA replication in eukaryotic cells and how these events are regulated

    Purification and functional inactivation of the fission yeast MCMMCM–BP complex

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    AbstractThe MCM (mini-chromosome maintenance) complex is the core of the eukaryotic replicative helicase and comprises six proteins, Mcm2–Mcm7. In humans, a variant form of the complex has Mcm2 replaced by the MCM–BP protein. Recent results suggest that a similar complex exists in fission yeast with an essential role in DNA replication and cell cycle progression. Here, we describe the purification and subunit composition of the fission yeast MCMMcb1 complex. Using newly generated temperature-sensitive alleles, we show that loss of MCMMcb1 function leads to accumulation of DNA damage, checkpoint activation and cell cycle arrest, and provide evidence for a role for MCMMcb1 in meiosis.Structured summary of protein interactionsMcb1 physically interacts with Mcm4 by pull down (View interaction)Mcb1 physically interacts with Mcm5 by pull down (View interaction)Mcb1 physically interacts with Mcm6 by pull down (View interaction)Mcm4 and Mcb1 physically interact by bimolecular fluorescence complementation (View interaction)Mcb1 physically interacts with Mcm3, Mcm4, Mcm5, Mcm6 and Mcm7 by tandem affinity purification (View interaction)Mcb1 physically interacts with Mcm7 by pull down (View interaction

    Tennessee roads / Jesse Stuart. In Mountain herald / Lincoln Memorial University.

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    This picturesque poem was written by then-sophomore (and future celebrated author) Jesse Stuart about the roads of Tennessee

    No. 617 Stuart Ruckman

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    Transcript (12, 40 pages) of two interviews by Matt Driscoll with Stuart Ruckman on April 9, 2010, and July 7, 2011Ruckman (b. 1966) was born in Salt Lake City, Utah. Stuart shares how his family, particularly his father, played a significant role in introducing him to the outdoors. Some of his initial explorations included a hike to the top of Mount Olympus when he was five years old, backpacking trips in the Wasatch and Uinta Mountains, and a successful summit attempt on the Grand Teton when he was twelve. Stuart discovered technical rock climbing due to the influence of his older brother Bret, five years Stuart\u27s senior. Bret learned under Dennis Turville, a well-respected Salt Lake climbing instructor. Stuart shares his observations on the Salt Lake climbing community of the late 1970s and 1980s, noting the intimacy of the community, while also pointing out the significant influence of a handful of climbers, including Merrill Bitter, Les Ellison, and Brian Smoot. He briefly describes the proliferation of new-route development in the Wasatch during his first decade in climbing. In collaboration with his brother Bret, Stuart published comprehensive guidebooks on climbing in the Wasatch Mountains. Stuart\u27s contributions as a first-ascensionist and co-author of Rock Climbing the Wasatch Range attest to his lasting impact on Utah climbing. Interview is part of the Outdoor Recreation History Project. Interviewer: Matt Driscol

    Genetics of lagging strand DNA synthesis and maturation in fission yeast:suppression analysis links the Dna2-Cdc24 complex to DNA polymerase delta

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    The Cdc24 protein is essential for the completion of chromosomal DNA replication in fission yeast. Although its precise role in this process is unclear, Cdc24 forms a complex with Dna2, a conserved endonuclease-helicase implicated in the removal of the RNA-DNA primer during Okazaki fragment processing. To gain further insights into Cdc24-Dna2 function, we screened for chromosomal suppressors of the temperature-sensitive cdc24-M38 allele and mapped the suppressing mutations into six complementation groups. Two of these mutations defined genes encoding the Pol3 and Cdc27 subunits of DNA polymerase delta. Sequence analysis revealed that all the suppressing mutations in Cdc27 resulted in truncation of the protein and loss of sequences that included the conserved C-terminal PCNA binding motif, previously shown to play an important role in maximizing enzyme processivity in vitro. Deletion of this motif is shown to be sufficient for suppression of both cdc24-M38 and dna2-C2, a temperature-sensitive allele of dna2(+), suggesting that disruption of the interaction between Cdc27 and PCNA renders the activity of the Cdc24-Dna2 complex dispensable.</p

    George MacLeod’s open-air preaching: performance and counter-performance

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    Stuart Blythe uses the methodology of performance to analyse George MacLeod’s open-air preaching. He points out that MacLeod’s preaching was derived from a theology of the incarnation, and an understanding of the paradoxes and dichotomies of common human life. This preaching, Blythe suggests, was also a counter-performance in the context of outlooks and ideologies inimical to the gospel. The paper raises interesting issues related to preaching as performance, and the further question as to whether or not the life and work of the Church as a whole might now be better understood as a counter-performance.Publisher PD

    The archaeo-eukaryotic GINS proteins and the archaeal primase catalytic subunit PriS share a common domain

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    This work was funded by the Scottish Universities Life Sciences Alliance (SULSA).Primase and GINS are essential factors for chromosomal DNA replication in eukaryotic and archaeal cells. Here we describe a previously undetected relationship between the C-terminal domain of the catalytic subunit (PriS) of archaeal primase and the B-domains of the archaeo-eukaryotic GINS proteins in the form of a conserved structural domain comprising a three-stranded antiparallel beta-sheet adjacent to an alpha-helix and a two-stranded beta-sheet or hairpin. The presence of a shared domain in archaeal PriS and GINS proteins, the genes for which are often found adjacent on the chromosome, suggests simple mechanisms for the evolution of these proteins.Peer reviewe

    Redemption in the work of Francis Stuart

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    The idea of redemption is central to an understanding of the work of Francis Stuart. Through an examination of its development and expression, it is possible to demonstrate the integrity of his work and its distinctive qualities. Such a demonstration is necessary because Stuart's writing has been subjected to comparatively little scholarly inquiry, although reviews of his work, especially that produced since 1949, suggest that it is impressive and important. First, a general background to Stuart's work, a discussion of the special problems associated with reading it, and a summary of his corpus is provided. This indicates that the idea of redemption is important to his earliest writing. The state of redemption is shown to be a necessary apotheosis for Stuart's outcast heroes; it involves spiritual suffering through which may be found a sense of reintegration and a higher reality. This is expressed through interrelated themes such as those of gambler, artist and ordinary man; mystic and criminal; sacred and profane love; and spirituality and the mundane. The nature of the redemptive experience is further elaborated by distinctive, complex motifs, especially the hare, the ark and the woman-Christ. Their recurrence provides an important element in the unity of Stuart's work. Because Stuart's idea of the outcast raises important biographical questions, an examination of the relationship between Stuart's life and his work is made. Finally, the way in which the idea of redemption exists in the language structures of Stuart's novels is examined, with especial reference to his most recent work, The High Consistory. The thesis shows that the development of the these of redemption demonstrates the integrity of Stuart's work

    John Stuart Mill’s projected science of society: 1827-1848

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    The purpose of the thesis is to examine John Stuart Mill’s political thought from about 1827 to 1848 as an exercise in intellectual history. It focuses, first, on Mill’s view, formulated by the late 1830s, that contemporary society was ‘civilized’, and second, on his project of a science of society, which he aspired to develop in the late 1830s and early 1840s. By the late 1830s, Mill came to the view that his contemporary society was a ‘commercial society or civilization’, dominated by the middle, commercial class. The first part of my thesis, constituted by Chapters 2-4, discusses the way in which Mill formed his notion of civilization, and what he meant by the term ‘civilization’. Mill paid attention to the implications of the rise of the middle class, and regarded such phenomena of contemporary society as the corruption of the commercial spirit and excessive social conformity as an inevitable consequence of the rise of the middle class. The second part of the thesis, constituted by Chapters 5-9, examines Mill’s projected science of society. In the late 1830s and early 1840s, Mill attempted to develop a new science of society whose subject-matter was the nature and prospects of commercial, civilized society. This aspiration culminated in A System of Logic, published in 1843. In examining Mill’s projected science, I pay particular attention to the fact that he conceived new sciences of history and of the formation of character, both of which were indispensable in his project, although he failed to give a complete account of these sciences. My thesis shows that the implications of his interest both in history and in the formation of character are more significant than Mill scholars have assumed

    An Evaluation of the Bush Administration Reforms to the Regulatory Process

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    The Bush Administration has implemented more reforms to the regulatory process than any of its predecessors. These reforms are often stereotyped as anti-regulatory. This article examines the reforms as a whole and asks which interests have been empowered by the Bush Administration regulatory reforms. I believe this method is a more effective way of assessing the impact of the reforms. I find that in addition to adding potential costs to the regulatory process, the reforms are likely to empower powerful interest groups and the presidency. Whether the impact of these reforms is pro-regulation or anti-regulation will depend on how a future administration more dedicated to regulatory protections uses them. I also lay out a research agenda to better empirically assess the impact of these regulatory reforms.Peer reviewed"Issue published online: 11 APR 2007. Article first published online: 11 APR 2007"--Publisher website
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