XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining

International audienceThe Ku70-Ku80 (Ku) heterodimer binds rapidly and tightly to the ends of DNA double-strand breaks and recruits factors of the non-homologous end-joining (NHEJ) repair pathway through molecular interactions that remain unclear. We have determined crystal structures of the Ku-binding motifs (KBM) of the NHEJ proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex. The two KBM motifs bind remote sites of the Ku80 alpha/beta domain. The X-KBM occupies an internal pocket formed by an unprecedented large outward rotation of the Ku80 alpha/beta domain. We observe independent recruitment of the APLF-interacting protein XRCC4 and of XLF to laser-irradiated sites via binding of A- and X-KBMs, respectively, to Ku80. Finally, we show that mutation of the X-KBM and A-KBM binding sites in Ku80 compromises both the efficiency and accuracy of end joining and cellular radiosensitivity. A- and X-KBMs may represent two initial anchor points to build the intricate interaction network required for NHEJ

Grand Challenges of Enterprise Integration

Enterprise Integration connects and combines people, processes, systems, and technologies to ensure that the right people and the right processes have the right information and the right resources at the right time. A consensus roadmap for Technologies for Enterprise Integration was created as part of an industry/government/academia partnership in the Integrated Manufacturing Technology Initiative (IMTI). Two of the grand challenges identified by the roadmapping effort will be addressed here--Customer Responsive Enterprises and Totally Connected Enterprises. Each of these challenges is briefly discussed as to the current state of industry and the future vision as developed in the roadmap

Assessment of impact damage in Kevlar{reg_sign}-epoxy, filament-wound spherical test specimens by acoustic emission techniques

The results of a study of the acoustic emission (AE) behavior of impact-damaged, spherical, composite test specimens subjected to thermal cycling and biaxial mechanical loading are presented. Seven Kevlar{reg_sign}-epoxy, filament-wound, spherical composite test specimens were subjected to different levels of impact damage. The seven specimens were a subset of a group of 77 specimens made with simulated fabrication-induced flaws. The specimens were subjected to two or three cycles of elevated temperature and then hydraulically pressurized to failure. The pressurization regime consisted of two cycles to different intermediate levels with a hold at each peak pressure level; a final pressurization to failure followed. The thermal and pressurization cycles were carefully designed to stimulate AE production under defined conditions. Both impacted and nonimpacted specimens produced thermo-AE (the term given to emission stimulated by thermal loading), but impacted specimens produced significantly more. Thermo-AE was produced primarily by damaged composite material. Damaged material produced emission as a function of both rising and falling temperature, but the effect was not repeatable. More seriously damaged specimens produced very large quantities of emission. Emission recorded during the static portion of the hydraulic loading cycles varied with load, time, and degree of damage. Static load AE behavior was quantified using a newly developed concept, the event-rate moment, and various correlations with residual strength were attempted. Correlations between residual strength, long-duration events, and even-rate moments were developed with varying degrees of success