Structural basis of TFIIH activation for nucleotide excision repair.

Nucleotide excision repair (NER) is the major DNA repair pathway that removes UV-induced and bulky DNA lesions. There is currently no structure of NER intermediates, which form around the large multisubunit transcription factor IIH (TFIIH). Here we report the cryo-EM structure of an NER intermediate containing TFIIH and the NER factor XPA. Compared to its transcription conformation, the TFIIH structure is rearranged such that its ATPase subunits XPB and XPD bind double- and single-stranded DNA, consistent with their translocase and helicase activities, respectively. XPA releases the inhibitory kinase module of TFIIH, displaces a 'plug' element from the DNA-binding pore in XPD, and together with the NER factor XPG stimulates XPD activity. Our results explain how TFIIH is switched from a transcription to a repair factor, and provide the basis for a mechanistic analysis of the NER pathway

Efficient Simulation of Chromatographic Processes Using the Conservation Element/Solution Element Method

Chromatographic separation processes need efficient simulation methods, especially for nonlinear adsorption isotherms such as the Langmuir isotherms which imply the formation of concentration shocks. The focus of this paper is on the space–time conservation element/solution element (CE/SE) method. This is an explicit method for the solution of systems of partial differential equations. Numerical stability of this method is guaranteed when the Courant–Friedrichs–Lewy condition is satisfied. To investigate the accuracy and efficiency of this method, it is compared with the classical cell model, which corresponds to a first-order finite volume discretization using a method of lines approach (MOL). The evaluation is done for different models, including the ideal equilibrium model and a mass transfer model for different adsorption isotherms—including linear and nonlinear Langmuir isotherms—and for different chromatographic processes from single-column operation to more sophisticated simulated moving bed (SMB) processes for the separation of binary and ternary mixtures. The results clearly show that CE/SE outperforms MOL in terms of computational times for all considered cases, ranging from 11-fold for the case with linear isotherm to 350-fold for the most complicated case with ternary center-cut eight-zone SMB with Langmuir isotherms, and it could be successfully applied for the optimization and control studies of such processes

Structural basis of human transcription–DNA repair coupling

Transcription-coupled DNA repair removes bulky DNA lesions from the genome1,2 and protects cells against ultraviolet (UV) irradiation3. Transcription-coupled DNA repair begins when RNA polymerase II (Pol II) stalls at a DNA lesion and recruits the Cockayne syndrome protein CSB, the E3 ubiquitin ligase, CRL4CSA and UV-stimulated scaffold protein A (UVSSA)3. Here we provide five high-resolution structures of Pol II transcription complexes containing human transcription-coupled DNA repair factors and the elongation factors PAF1 complex (PAF) and SPT6. Together with biochemical and published3,4 data, the structures provide a model for transcription–repair coupling. Stalling of Pol II at a DNA lesion triggers replacement of the elongation factor DSIF by CSB, which binds to PAF and moves upstream DNA to SPT6. The resulting elongation complex, ECTCR, uses the CSA-stimulated translocase activity of CSB to pull on upstream DNA and push Pol II forward. If the lesion cannot be bypassed, CRL4CSA spans over the Pol II clamp and ubiquitylates the RPB1 residue K1268, enabling recruitment of TFIIH to UVSSA and DNA repair. Conformational changes in CRL4CSA lead to ubiquitylation of CSB and to release of transcription-coupled DNA repair factors before transcription may continue over repaired DNA

Dynamic Nonlinear X-waves for Femtosecond Pulse Propagation in Water

Recent experiments on femtosecond pulses in water displayed long distance propagation analogous to that reported in air. We verify this phenomena numerically and show that the propagation is dynamic as opposed to self-guided. Furthermore, we demonstrate that the propagation can be interpreted as due to dynamic nonlinear X-waves whose robustness and role in long distance propagation is shown to follow from the interplay between nonlinearity and chromatic dispersion.Comment: 4 page

The hRPC62 subunit of human RNA polymerase III displays helicase activity.

In Eukaryotes, tRNAs, 5S RNA and U6 RNA are transcribed by RNA polymerase (Pol) III. Human Pol III is composed of 17 subunits. Three specific Pol III subunits form a stable ternary subcomplex (RPC62-RPC39-RPC32α/β) being involved in pre-initiation complex formation. No paralogues for subunits of this subcomplex subunits have been found in Pols I or II, but hRPC62 was shown to be structurally related to the general Pol II transcription factor hTFIIEα. Here we show that these structural homologies extend to functional similarities. hRPC62 as well as hTFIIEα possess intrinsic ATP-dependent 3'-5' DNA unwinding activity. The ATPase activities of both proteins are stimulated by single-stranded DNA. Moreover, the eWH domain of hTFIIEα can replace the first eWH (eWH1) domain of hRPC62 in ATPase and DNA unwinding assays. Our results identify intrinsic enzymatic activities in hRPC62 and hTFIIEα

Donor-acceptor recombination emission in hydrogen-terminated nanodiamond: Novel single-photon source for room-temperature quantum photonics

In fluorescence spectra of nanodiamonds (NDs) synthesized at high pressure from adamantane and other organic compounds, very narrow (~1 nm) lines of unknown origin are observed in a wide spectroscopic range from ~500 to 800 nm. Here, we propose and experimentally substantiate the hypothesis that these mysterious lines arise from radiative recombination of donor-acceptor pairs (DAPs). To confirm our hypothesis, we study the fluorescence spectra of undoped and nitrogen-doped NDs of different sizes, before and after thermal oxidation of their surface. The results obtained with a high degree of confidence allowed us to conclude that the DAPs are formed through the interaction of donor-like substitutional nitrogen present in the diamond lattice, and a 2D layer of acceptors resulting from the transfer doping effect on the surface of hydrogen-terminated NDs. A specific behavior of the DAP-induced lines was discovered in the temperature range of 100-10 K: their energy increases and most lines are split into 2 or more components with decreasing temperature. It is shown that the majority of the studied DAP emitters are sources of single photons, with an emission rate of up to >1 million counts/s at room temperature, which significantly surpasses that of nitrogen-vacancy and silicon-vacancy centers under the same detection conditions. Despite an observed temporal instability in the emission, the DAP emitters of H-terminated NDs represent a powerful room-temperature single-photon source for quantum optical technologies

On the Properties of Two Pulses Propagating Simultaneously in Different Dispersion Regimes in a Nonlinear Planar Waveguide

Properties of two pulses propagating simultaneously in different dispersion regimes, anomalous and normal, in a Kerr-type planar waveguide are studied in the framework of the nonlinear Schroedinger equation. Catastrophic self-focusing and spatio-temporal splitting of the pulses is investigated. For the limiting case when the dispersive term of the pulse propagating in the normal dispersion regime can be neglected an indication of a possibility of a stable self-trapped propagation of both pulses is obtained.Comment: 18 pages (including 15 eps figures

X-wave mediated instability of plane waves in Kerr media

Plane waves in Kerr media spontaneously generate paraxial X-waves (i.e. non-dispersive and non-diffractive pulsed beams) that get amplified along propagation. This effect can be considered a form of conical emission (i.e. spatio-temporal modulational instability), and can be used as a key for the interpretation of the out of axis energy emission in the splitting process of focused pulses in normally dispersive materials. A new class of spatio-temporal localized wave patterns is identified. X-waves instability, and nonlinear X-waves, are also expected in periodical Bose condensed gases.Comment: 4 pages, 6 figure