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The Invention of Tradition
Many of the traditions which we think of as very ancient in their origins were not in fact sanctioned by long usage over the centuries, but were invented comparatively recently. This book explores examples of this process of invention – the creation of Welsh and Scottish 'national culture'; the elaboration of British royal rituals in the nineteenth and twentieth centuries; the origins of imperial rituals in British India and Africa; and the attempts by radical movements to develop counter-traditions of their own. It addresses the complex interaction of past and present, bringing together historians and anthropologists in a fascinating study of ritual and symbolism which poses new questions for the understanding of our history.
eBook
A brief history of creation : science and the search for the origin of life
An essential history of Western scientific studies into the origins of life examines historical discoveries in the contexts of philosophical debates, political change, and evolving understandings about the complexities of biology.
BOOK
Establishment and function of chromatin organization at replication origins
The origin recognition complex (ORC) is essential for initiation of eukaryotic chromosome replication as it loads the replicative helicase—the minichromosome maintenance (MCM) complex—at replication origins
1
. Replication origins display a stereotypic nucleosome organization with nucleosome depletion at ORC-binding sites and flanking arrays of regularly spaced nucleosomes
2
–
4
. However, how this nucleosome organization is established and whether this organization is required for replication remain unknown. Here, using genome-scale biochemical reconstitution with approximately 300 replication origins, we screened 17 purified chromatin factors from budding yeast and found that the ORC established nucleosome depletion over replication origins and flanking nucleosome arrays by orchestrating the chromatin remodellers INO80, ISW1a, ISW2 and Chd1. The functional importance of the nucleosome-organizing activity of the ORC was demonstrated by
orc1
mutations that maintained classical MCM-loader activity but abrogated the array-generation activity of ORC. These mutations impaired replication through chromatin in vitro and were lethal in vivo. Our results establish that ORC, in addition to its canonical role as the MCM loader, has a second crucial function as a master regulator of nucleosome organization at the replication origin, a crucial prerequisite for efficient chromosome replication.
Genome-scale in vitro reconstitution of DNA replication through chromatin establishes a crucial role for the origin recognition complex in organizing nucleosome arrays that are crucial for the initiation of replication.
Journal Article
Structure of the origin recognition complex bound to DNA replication origin
The six-subunit origin recognition complex (ORC) binds to DNA to mark the site for the initiation of replication in eukaryotes. Here we report a 3 Å cryo-electron microscopy structure of the
Saccharomyces cerevisiae
ORC bound to a 72-base-pair origin DNA sequence that contains the ARS consensus sequence (ACS) and the B1 element. The ORC encircles DNA through extensive interactions with both phosphate backbone and bases, and bends DNA at the ACS and B1 sites. Specific recognition of thymine residues in the ACS is carried out by a conserved basic amino acid motif of Orc1 in the minor groove, and by a species-specific helical insertion motif of Orc4 in the major groove. Moreover, similar insertions into major and minor grooves are also embedded in the B1 site by basic patch motifs from Orc2 and Orc5, respectively, to contact bases and to bend DNA. This work pinpoints a conserved role of ORC in modulating DNA structure to facilitate origin selection and helicase loading in eukaryotes.
The cryo-EM structure of the yeast origin recognition complex (ORC) bound to a 72-base-pair origin DNA sequence provides insights into the basis of the origin selection mechanism.
Journal Article
Replication landscape of the human genome
Despite intense investigation, human replication origins and termini remain elusive. Existing data have shown strong discrepancies. Here we sequenced highly purified Okazaki fragments from two cell types and, for the first time, quantitated replication fork directionality and delineated initiation and termination zones genome-wide. Replication initiates stochastically, primarily within non-transcribed, broad (up to 150 kb) zones that often abut transcribed genes, and terminates dispersively between them. Replication fork progression is significantly co-oriented with the transcription. Initiation and termination zones are frequently contiguous, sometimes separated by regions of unidirectional replication. Initiation zones are enriched in open chromatin and enhancer marks, even when not flanked by genes, and often border ‘topologically associating domains’ (TADs). Initiation zones are enriched in origin recognition complex (ORC)-binding sites and better align to origins previously mapped using bubble-trap than λ-exonuclease. This novel panorama of replication reveals how chromatin and transcription modulate the initiation process to create cell-type-specific replication programs.
The physical origin and termination sites of DNA replication in human cells have remained elusive. Here the authors use Okazaki fragment sequencing to reveal global replication patterns and show how chromatin and transcription modulate the process.
Journal Article