Repeat tracts of guanine bases found in DNA and RNA can form tetraplex structures in the presence of a variety of monovalent cations. Evidence suggests that guanine tetraplexes assume important functions within chromosomal telomeres, immunoglobulin switch regions, and the human immunodeficiency virus genome. The structure of a parallel-stranded tetraplex formed by the hexanucleotide d(TG4T) and stabilized by sodium cations was determined by x-ray crystallography to 1.2 angstroms resolution. Sharply resolved sodium cations were found between and within planes of hydrogen-bonded guanine quartets, and an ordered groove hydration was observed. Distinct intra- and intermolecular stacking arrangements were adopted by the guanine quartets. Thymine bases were exclusively involved in making extensive lattice contacts.

The mutagenic and carcinogenic effects of simple alkylating agents are mainly due to methylation at the O6 position of guanine in DNA. O6‐methylguanine directs the incorporation of either thymine or cytosine without blocking DNA replication, resulting in GC to AT transition mutations. In prokaryotic and eukaryotic cells antimutagenic repair is effected by direct reversal of this DNA damage. A suicidal methyltransferase repair protein removes the methyl group from DNA to one of its own cysteine residues. The resulting self‐methylation of the active site cysteine renders the protein inactive. Here we report the X‐ray structure of the 19 kDa C‐terminal domain of the Escherichia coli ada gene product, the prototype of these suicidal methyltransferases. In the crystal structure the active site cysteine is buried. We propose a model for the significant conformational change that the protein must undergo in order to bind DNA and effect methyl transfer.

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Europa is unique in the solar system, having a young, icy surface bombarded by high-energy radiation and possessing many possible sources of surface material. One possible source is Europa's putative subsurface ocean, from which material may be emplaced through cryovolcanic activity or effusive flows. Impact ejecta from Io and implantation of iogenic sulfur, oxygen, sodium, potassium, and chlorine ions on Europa's trailing hemisphere are likely sources, as well as direct meteoritic and cometary impacts and outer-satellite-derived impact ejecta that spiral toward Jupiter. While we cannot yet answer the central question of where the non-ice material on Europa's surface comes from, we can identify and quantify the species that are known or thought to be present: H 2 O, a hydrate, SO 2 , elemental sulfur, O 2 , H 2 O 2 , CO 2 , Na, and K. Europa, like many satellites, has a hemispherical dichotomy, in this case a reddish trailing hemisphere (in the sense of orbital motion) and a brighter, leading hemisphere. The purest H 2 O is found on the leading hemisphere while the trailing hemisphere contains the highest concentration of the next most prevalent species, a hydrated material of unknown composition. The H 2 O ice on the leading side is amorphous on the upper surface, with crystalline ice present at submillimeter depths. The trailing hemisphere contains ice plus a hydrated component that may be hydrated salts, derived from the ocean as brine, and/or hydrated sulfuric acid, the major equilibrium product from radiolysis of sulfurous material and H 2 O. The source of sulfurous material could be endogenic or from implantation of iogenic sulfur, or both. Sulfur dioxide and sulfur are thought to be present, mainly on the trailing hemisphere. This is consistent with ion implantation, but the sulfur distribution and that of the hydrate show correlations with geological features, so there must be some endogenic control of these constituents, either as a source or modification process. All the species in the ~1-m regolith are affected by radiation, but the archetypal radiolytic species, observed on both hemispheres, are molecular oxygen and hydrogen peroxide. These are certainly radiolytic products since continuous production is required, with O 2 being volatile and escaping easily, while H 2 O 2 is quickly destroyed by sunlight. Carbon dioxide is present and poses a mystery. It could be outgassing from the interior or a photolytic or radiolytic product of micrometeorite-derived carbonaceous material. Sodium and potassium atoms are found in the tenuous atmosphere and arise from sputtering of surface material. These atoms can be derived initially from the iogenic plasma and from endogenic salts, but the implantation flux rates are not known well enough to establish the source. *Average mass influx from Cooper et al. (2001). Relative composition from Anders and Grevasse (1989). † Sulfur flux value from Johnson et al. (2004) for trailing side apex and based on Bagenal (1994). No plasma deflection is included. ‡ Equatorial mass i...

The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER is a member of the nuclear hormone receptor superfamily of transcription factors that requires co-regulator proteins for complete regulation. Emerging evidence has implicated a small number of histone methyltransferase (HMT) and histone demethylase (HDM) enzymes as regulators of ER signalling, including the histone H3 lysine 9 tri-/di-methyl HDM enzyme KDM4B. Two recent independent reports have demonstrated that KDM4B is required for ER-mediated transcription and depletion of the enzyme attenuates BCa growth in vitro and in vivo. Here we show that KDM4B has an overarching regulatory role in the ER signalling cascade by controlling expression of the ER and FOXA1 genes, two critical components for maintenance of the estrogen-dependent phenotype. KDM4B interacts with the transcription factor GATA-3 in BCa cell lines and directly co-activates GATA-3 activity in reporter-based experiments. Moreover, we reveal that KDM4B recruitment and demethylation of repressive H3K9me3 marks within upstream regulatory regions of the ER gene permits binding of GATA-3 to drive receptor expression. Ultimately, our findings confirm the importance of KDM4B within the ER signalling cascade and as a potential therapeutic target for BCa treatment.