The structure of DNA in the nucleosome core

Richmond, Timothy J.; Davey, C.A.

doi:10.1038/nature01595

Cited by 1,156 publications

(1,151 citation statements)

References 37 publications

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“…For example, the catabolic activator protein (CAP) introduces two sharp kinks at pyrimidine-purine (YR) steps in its binding site, bending the DNA at these steps into the major groove via large positive roll 57,58 . By contrast, the DNA wrapped tightly around the assembly of histone proteins on the surface of the nucleosome core particle deforms via both positive and negative roll, with pronounced bending into the minor groove occurring at regularly spaced YR steps 59 . In between these two extremes of bending are other possible modes of deformation, such as the patterns of roll in the idealized curved DNA pathways presented in the Calladine et al textbook on DNA structural mechanics 60 .…”

Section: Sample Applications Of 3dnamentioning

confidence: 98%

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

2008

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We present a set of protocols showing how to use the 3DNA suite of programs to analyze, rebuild, and visualize three-dimensional nucleic-acid structures. The software determines a wide range of conformational parameters, including the identities and rigid-body parameters of interacting bases and base-pair steps, the nucleotides comprising helical fragments, the area of overlap of stacked bases, etc. The reconstruction of three-dimensional structure takes advantage of rigorously defined rigid-body parameters, producing rectangular block representations of the nucleic-acid bases and base pairs and all-atom models with approximate sugar-phosphate backbones. The visualization components create vector-based drawings and scenes that can be rendered as raster-graphics images, allowing for easy generation of publication-quality figures. The utility programs use geometric variables to control the view and scale of an object, for comparison of related structures. The commands run in seconds even for large structures. The software and related information are available at http://3dna.rutgers.edu/.

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Section: Sample Applications Of 3dnamentioning

confidence: 98%

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

2008

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“…They can generate docking sites for interaction with additional proteins; bromo-, chromo-and SANT-domains have been shown to recognize specifically modified histones, and to mediate the recruitment of accessory regulatory factors that contain those domains. Also, modifications of histones might affect the condensation state and higher order chromatin structure, owing to their capacity to modulate the exposure of charge patches on the surface of the nucleosomes [5][6][7] .…”

Section: At a Glancementioning

confidence: 99%

“…The tail region of the histones (which extend away from the nucleosome core) undergo a complex and coordinated series of regulatory modifications [5][6][7] . These modifications can also occur within the globular domain of histones that make extensive contacts with DNA ( see FIG.…”

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Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer

2006

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| Histone deacetylases (HDACs) are considered to be among the most promising targets in drug development for cancer therapy, and first-generation histone deacetylase inhibitors (HDACi) are currently being tested in phase I/II clinical trials. A wide-ranging knowledge of the role of HDACs in tumorigenesis, and of the action of HDACi, has been achieved. However, several basic aspects are not yet fully understood. Investigating these aspects in the context of what we now understand about HDACi action both in vitro and in vivo will further improve the design of optimized clinical protocols.Histone deacetylases (HDACs) have been intensively scrutinized over the past few years for two main reasons. First, they have been linked mechanistically to the pathogenesis of cancer, as well as several other diseases. Second, small-molecule HDAC inhibitors (HDACi) exist that have the capacity to interfere with HDAC activity and can therefore achieve significant biological effects in preclinical models of cancer. These findings justified the introduction of HDACi into clinical trials. These initial clinical trials have just ended and show encouraging results. At this stage it is crucial to evaluate whether our current knowledge on the mechanisms of tumorigenesis that are linked to HDACs, and on the mechanisms of tumour sensitivity to HDACi, is firm enough to improve the design of further clinical trials. Recent structural and chemical data have emerged that will help in the design of novel HDACi with more desirable properties than the existing ones. However, key areas of investigation that might help to further illuminate the design of successful HDACi-based cancer therapy remain poorly explored. Novel findings indicate that our understanding of how HDACi work will probably change significantly, establishing a new paradigm in the field of intelligent drug design with broad implications for the design of targeted therapies in cancer and possibly other diseases.HDACs: enzymes looking for substrate(s) Four HDAC classes have been identified (FIG. 1a). One of them (class 3 or the so-called sirtuins, from the yeast protein Sir2) constitutes a structurally unrelated, NADdependent subfamily, and will not be considered here; neither will the class 3-specific HDACi, which are less characterized than those for the other classes 1 .An extensive phylogenetic analysis of HDACs has been performed 2,3 . HDACs are members of an ancient enzyme family found in animals, plants, fungi and bacteria. It is thought that HDACs evolved in the absence of histone proteins. Indeed, eukaryotic HDACs can deacetylate non-histone as well as histone substrates, and some HDACs reside in the cytoplasm (where histones are synthesized and acetylated for proper assembly, without the intervention of HDACs) and in mitochondria (where histones are absent).Are HDACs, then, truly HDACs 4 ? We postulate that key HDAC substrates might not be histones, but instead belong to the growing list of acetylated non-histone proteins (FIG. 1b and Supplementary information S1 ...

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“…In chromatin, DNA is folded in a hierarchical fashion. At the first level, 147 bp of DNA is wrapped around an octamer of four histone proteins (two molecules each of the four core histones H2A, H2B, H3, and H4) to form the nucleosome core particle [Kornberg, 1974;Luger et al, 1997;Richmond and Davey, 2003]. The resulting ''beadson-a-string'' configuration is sometimes referred to as the ''10-nm fiber.''…”

Section: Introductionmentioning

confidence: 99%

The γ‐H2A.X: Is it just a surrogate marker of double‐strand breaks or much more?

Ismail

Hendzel

2007

Environ and Mol Mutagen

100

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In recent years, several histone modifications have been implicated in the cellular response to DNA double-strand breaks (DSBs). One of the best characterized histone modifications important in DSB repair is the phosphorylation of histone H2A variant, H2A.X. In response to DSBs, H2A.X is phosphorylated and this phosphorylation is required for DSB signaling and the retention of repair proteins at the break site. Despite the existing picture that the function of H2A.X is to promote DNA repair, very recent data suggest that the phosphorylation of histone H2A.X has additional functions. This is analogous to histone H3 phosphorylation on serine 10, which participates in seemingly incompatible functions-transcriptional activation and mitosis. In this review, we discuss the role of histone H2A.X in maintaining genomic stability and review emerging evidence that histone H2A.X is multifunctional. Environ. Mol. Mutagen. 49:73-82, 2008. V V C 2007 Wiley-Liss, Inc.

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The structure of DNA in the nucleosome core

Cited by 1,156 publications

References 37 publications

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer

The γ‐H2A.X: Is it just a surrogate marker of double‐strand breaks or much more?

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