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Wanotayan R.,Research Laboratory for Nuclear Reactors | Fukuchi M.,Research Laboratory for Nuclear Reactors | Imamichi S.,Research Laboratory for Nuclear Reactors | Imamichi S.,National Cancer Institute Research Institute | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

XRCC4 is one of the crucial proteins in the repair of DNA double-strand break (DSB) through non-homologous end-joining (NHEJ). As XRCC4 consists of 336 amino acids, N-terminal 200 amino acids include domains for dimerization and for association with DNA ligase IV and XLF and shown to be essential for XRCC4 function in DSB repair and V(D)J recombination. On the other hand, the role of the remaining C-terminal region of XRCC4 is not well understood. In the present study, we noticed that a stretch of ∼20 amino acids located at the extreme C-terminus of XRCC4 is highly conserved among vertebrate species. To explore its possible importance, series of mutants in this region were constructed and assessed for the functionality in terms of ability to rescue radiosensitivity of M10 cells lacking XRCC4. Among 13 mutants, M10 transfectant with N326L mutant (M10-XRCC4N326L) showed elevated radiosensitivity. N326L protein showed defective nuclear localization. N326L sequence matched the consensus sequence of nuclear export signal. Leptomycin B treatment accumulated XRCC4N326L in the nucleus but only partially rescued radiosensitivity of M10-XRCC4N326L. These results collectively indicated that the functional defects of XRCC4N326L might be partially, but not solely, due to its exclusion from nucleus by synthetic nuclear export signal. Further mutation of XRCC4 Asn326 to other amino acids, i.e., alanine, aspartic acid or glutamine did not affect the nuclear localization but still exhibited radiosensitivity. The present results indicated the importance of the extremely C-terminal region of XRCC4 and, especially, Asn326 therein. © 2015 Elsevier Inc.

Hasegawa J.,Tokyo Institute of Technology | Kondo K.,Research Laboratory for Nuclear Reactors | Oguri Y.,Research Laboratory for Nuclear Reactors | Horioka K.,Tokyo Institute of Technology
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2014

Beam focusing properties of cone optics were systematically investigated by Monte Carlo simulations under various combinations of beam and cone parameters. To optimize the cone optic design for accelerator-driven WDM experiments, the beam intensity gains after cone focusing were evaluated from the simulation results as functions of cone wall material and shape parameters such as taper angle and wall curvature. The uniformity of the cone-focused beam was also examined by considering not only various cone parameters but also the cases involving the misalignment of the cone optic. From the results, a parabolic gold cone was found to be the best choice at least for relatively light ions such as lithium having MeV energies. It is also found that although smaller taper angle improves the total beam transport efficiency in the optic, it brings more difficulties in the alignment of the optic because the alignment accuracy should be less than a half of the taper angle to obtain acceptable uniformity in the beam energy deposition on the target. © 2013 Elsevier B.V.

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