Loss of the methylarginine reader function of SND1 confers resistance to hepatocellular carcinoma.

Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that 'reads' methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed to promote HCC.

Direct Regulation of DNA Repair by E2F and RB in Mammals and Plants: Core Function or Convergent Evolution?

Members of the E2F transcription factor family regulate the expression of genes important for DNA replication and mitotic cell division in most eukaryotes. Homologs of the retinoblastoma (RB) tumor suppressor inhibit the activity of E2F factors, thus controlling cell cycle progression. Organisms such as budding and fission yeast have lost genes encoding E2F and RB, but have gained genes encoding other proteins that take on E2F and RB cell cycle-related functions.

The E2F1 transcription factor and RB tumor suppressor moonlight as DNA repair factors.

The E2F1 transcription factor and RB tumor suppressor are best known for their roles in regulating the expression of genes important for cell cycle progression but, they also have transcription-independent functions that facilitate DNA repair at sites of damage. Depending on the type of DNA damage, E2F1 can recruit either the GCN5 or p300/CBP histone acetyltransferases to deposit different histone acetylation marks in flanking chromatin. At DNA double-strand breaks, E2F1 also recruits RB and the BRG1 ATPase to remodel chromatin and promote loading of the MRE11-RAD50-NBS1 complex.

E2F1 acetylation directs p300/CBP-mediated histone acetylation at DNA double-strand breaks to facilitate repair.

E2F1 and retinoblastoma (RB) tumor-suppressor protein not only regulate the periodic expression of genes important for cell proliferation, but also localize to DNA double-strand breaks (DSBs) to promote repair. E2F1 is acetylated in response to DNA damage but the role this plays in DNA repair is unknown. Here we demonstrate that E2F1 acetylation creates a binding motif for the bromodomains of the p300/KAT3B and CBP/KAT3A acetyltransferases and that this interaction is required for the recruitment of p300 and CBP to DSBs and the induction of histone acetylation at sites of damage.

The Retinoblastoma (RB) Tumor Suppressor: Pushing Back against Genome Instability on Multiple Fronts.

The retinoblastoma (RB) tumor suppressor is known as a master regulator of the cell cycle. RB is mutated or functionally inactivated in the majority of human cancers. This transcriptional regulator exerts its function in cell cycle control through its interaction with the E2F family of transcription factors and with chromatin remodelers and modifiers that contribute to the repression of genes important for cell cycle progression.

The p53 R72P polymorphism does not affect the physiological response to ionizing radiation in a mouse model.

Tissue culture and mouse model studies show that the presence of the arginine (R) or proline (P) coding single nucleotide polymorphism (SNP) of the tumor suppressor gene p53 at codon 72 (p53 R72P) differentially affects the responses to genotoxic insult. Compared to the P variant, the R variant shows increased apoptosis in most cell cultures and mouse model tissues in response to genotoxins, and epidemiological studies suggest that the R variant may enhance cancer survival and reduce the risks of adverse reactions to genotoxic cancer treatment. As ionizing radiation (IR) treatment is often used in cancer therapy, we sought to test the physiological effects of IR in mouse models of the p53 R72P polymorphism.

RB localizes to DNA double-strand breaks and promotes DNA end resection and homologous recombination through the recruitment of BRG1.

The retinoblastoma (RB) tumor suppressor is recognized as a master regulator that controls entry into the S phase of the cell cycle. Its loss leads to uncontrolled cell proliferation and is a hallmark of cancer. RB works by binding to members of the E2F family of transcription factors and recruiting chromatin modifiers to the promoters of E2F target genes.

TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1.

DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy.

Structure of Amido Pyridinium Betaines: Persistent Intermolecular C-H⋅⋅⋅N Hydrogen Bonding in Solution.

A hydrogen bond of the type C-H⋅⋅⋅X (X=O or N) is known to influence the structure and function of chemical and biological systems in solution. C-H⋅⋅⋅O hydrogen bonding in solution has been extensively studied, both experimentally and computationally, whereas the equivalent thermodynamic parameters have not been enumerated experimentally for C-H⋅⋅⋅N hydrogen bonds. This is, in part, due to the lack of systems that exhibit persistent C-H⋅⋅⋅N hydrogen bonds in solution.

Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols: Experimental and Computational Study.

Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer.

Gold-Catalyzed Proto- and Deuterodeboronation.

A mild gold-catalyzed protodeboronation reaction, which does not require acid or base additives and can be carried out in "green" solvents, is described. As a result, the reaction is very functional-group-tolerant, even to acid- and base-sensitive functional groups, and should allow for the boronic acid group to be used as an effective traceless directing or blocking group. The reaction has also been extended to deuterodeboronations for regiospecific ipso-deuterations of aryls and heteroaryls from the corresponding organoboronic acid.

Far-infrared spectroscopy of the troposphere: calibration with a cold background.

The far-infrared spectroscopy of the troposphere (FIRST) instrument is a Fourier-transform spectrometer developed to measure the Earth's thermal emission spectrum with a particular emphasis on the far-infrared. FIRST has observed the atmosphere from both the ground looking up and from a high-altitude balloon looking down. A recent absolute laboratory calibration of FIRST under ground-like operating conditions showed accuracy to better than 0.

Palladium-catalyzed direct C-H functionalization of benzoquinone.

A direct Pd-catalyzed C-H functionalization of benzoquinone (BQ) can be controlled to give either mono- or disubstituted BQ, including the installation of two different groups in a one-pot procedure. BQ can now be directly functionalized with aryl, heteroaryl, cycloalkyl, and cycloalkene groups and, moreover, the reaction is conducted in environmentally benign water or acetone as solvents.

Gold(I)-catalysed direct thioetherifications using allylic alcohols: an experimental and computational study.

A gold(I)-catalysed direct thioetherification reaction between allylic alcohols and thiols is presented. The reaction is generally highly regioselective (S(N)2'). This dehydrative allylation procedure is very mild and atom economical, producing only water as the by-product and avoiding any unnecessary waste/steps associated with installing a leaving or activating group on the substrate.

E2F1 responds to ultraviolet radiation by directly stimulating DNA repair and suppressing carcinogenesis.

In response to DNA damage, the E2F1 transcription factor is phosphorylated at serine 31 (serine 29 in mouse) by the ATM or ATR kinases, which promotes E2F1 protein stabilization. Phosphorylation of E2F1 also leads to the recruitment of E2F1 to sites of DNA damage, where it functions to enhance DNA repair. To study the role of this E2F1 phosphorylation event in vivo, a knock-in mouse model was generated, in which serine 29 was mutated to alanine.

Identification of prohibitin and prohibiton as novel factors binding to the p53 induced gene 3 (PIG3) promoter (TGYCC)(15) motif.

The promoter of p53 induced gene 3 (PIG3) contains a variable number of tandem repeats (VNTRs) of pentanucleotides (TGYCC)n that is known as a p53 binding site. In this study, we investigated whether other potential molecules could bind to this PIG3 promoter (TGYCC)n motif. Ligand-chromatography combined with liquid chromatography-tandem mass spectrometry analyses indicated direct interactions of prohibitin and/or prohibiton with the (TGYCC)15 motif, which was confirmed by electrophoretic mobility shift assay and super-gel shift analysis with anti-prohibitin and anti-prohibiton antibodies.

Modeling gene-environment interactions in oral cavity and esophageal cancers demonstrates a role for the p53 R72P polymorphism in modulating susceptibility.

A large number of epidemiological studies have linked a common single-nucleotide polymorphism (SNP) in the human p53 gene to risk for developing a variety of cancers. This SNP encodes either an arginine or proline at position 72 (R72P) of the p53 protein, which can alter the apoptotic activity of p53 via transcriptional and non-transcriptional mechanisms. This SNP has also been reported to modulate the development of human papilloma virus (HPV)-driven cancers through differential targeting of the p53 variant proteins by the E6 viral oncoprotein.

Chromatin: receiver and quarterback for cellular signals.

Signal transduction pathways converge upon sequence-specific DNA binding factors to reprogram gene expression. Transcription factors, in turn, team up with chromatin modifying activities. However, chromatin is not simply an endpoint for signaling pathways.

Far-infrared spectroscopy of the troposphere: instrument description and calibration performance.

The far-infrared spectroscopy of the troposphere (FIRST) instrument is a Fourier transform spectrometer developed to measure the Earth's thermal emission spectrum with a particular emphasis on far-infrared (far-IR) wavelengths greater than 15 μm. FIRST was developed under NASA's Instrument Incubator Program to demonstrate technology for providing measurements from 10 to 100 μm (1000 to 100 cm(-1)) on a single focal plane with a spectral resolution finer than 1 cm(-1). Presently no spectrometers in orbit are capable of directly observing the Earth's far-IR spectrum.

Ruthenium-mediated C-H functionalization of pyridine: the role of vinylidene and pyridylidene ligands.

A combined experimental and theoretical study has demonstrated that [Ru(η(5)-C(5)H(5))(py)(2)(PPh(3))](+) is a key intermediate, and active catalyst for, the formation of 2-substituted E-styrylpyridines from pyridine and terminal alkynes HC≡CR (R = Ph, C(6)H(4)-4-CF(3)) in a 100% atom efficient manner under mild conditions. A catalyst deactivation pathway involving formation of the pyridylidene-containing complex [Ru(η(5)-C(5)H(5))(κ(3)-C(3)-C(5)H(4)NCH═CHR)(PPh(3))](+) and subsequently a 1-ruthanaindolizine complex has been identified. Mechanistic studies using (13)C- and D-labeling and DFT calculations suggest that a vinylidene-containing intermediate [Ru(η(5)-C(5)H(5))(py)(═C═CHR)(PPh(3))](+) is formed, which can then proceed to the pyridylidene-containing deactivation product or the desired product depending on the reaction conditions.

E2F1 and p53 transcription factors as accessory factors for nucleotide excision repair.

Many of the biochemical details of nucleotide excision repair (NER) have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure.

Absolute linearity measurement of photodetectors using sinusoidal modulated radiation.

A method is presented for characterizing the linearity of photodetectors based on time-domain analysis of response to sinusoidal excitation. Nonlinearity is quantified solely from the output distortion. Relative response is converted to absolute response by including two calibration points.

Charged behaviour from neutral ligands: synthesis and properties of N-heterocyclic pseudo-amides.

Deprotonation of the 1-isopropyl-3-(phenylamino)pyridin-1-ium iodide gives the corresponding neutral betaine, which is formalised as a pyridinium-amido ligand when coordinated to a metal. Spectroscopic, structural and theoretical methods have been used to investigate the metal-ligand bonding, ligand dynamics and electron distribution. Collectively, the data show that the ligand can be characterised as a pseudo-amide and is a strong donor akin to alkyl phosphines and N-heterocyclic carbenes.