Summary During DNA double strand break (DSB) repair, the ring-shaped Ku70/80 complex becomes trapped on DNA and needs to be actively extracted, but it has remained unclear what provides the required energy. By means of reconstitution of DSB repair on beads, we demonstrate here that DNA-locked Ku rings are released by the AAA-ATPase, p97. To achieve this, p97 requires ATP hydrolysis, cooperates with the Ufd1-Npl4 ubiquitin adapter complex and specifically targets Ku80 that is modified by K48-linked ubiquitin chains. In U2OS cells, chemical inhibition of p97, or siRNA-mediated depletion of p97 or its adapters impairs Ku80 removal after non-homologous end-joining of DSBs. Moreover, it attenuates early steps in homologous recombination consistent with p97-driven Ku release also affecting repair pathway choice. Thus, our data solve a central question regarding regulation of Ku in DSB repair, and illustrate the ability of p97 to segregate even tightly bound protein complexes for release from DNA.

Cations leaking through the voltage sensor of mutant sodium or calcium channels underlie hypokalaemic periodic paralysis. Groome et al. use muscle fibre recordings, voltage clamp, and molecular dynamics, to investigate recently discovered Nav1.4 channel mutations. They identify a novel voltage sensor movement that may explain the muscle pathology.

Urocanic acid (UCA) is a major UV chromophore in the upper layers of the skin where it is found predominantly as the trans isomer. UV irradiation induces photoisomerisation of trans-UCA to cis-UCA which has been shown to mimic some of the immunosuppressive properties of UV exposure. We examined the wavelength dependence for trans-UCA to cis-UCA photoisomerisation in vitro and in mouse skin in vivo over the spectral range 270-340 nm. The resulting action spectra were very similar with maximal effectiveness at 300-315 nm and equal activity at 270 nm and 325-330 nm, demonstrating that UVA-II radiation (320-340 nm) is efficient at UCA photoisomerisation. These action spectra differed markedly from the trans-UCA absorption spectrum in vitro and also the reported action spectrum for UV suppression of contact hypersensitivity in mice. These findings suggest that the relationship between cis-UCA formation in skin and UV-induced immunosuppression may be complex.

Mononitrosyl-iron compounds (MNICs) of the Enemark-Feltham {FeNO} 7 type can be divided into ad oublet (S = 1/2) and aq uartet (S = 3/2) spin variant. The latter relies on weak-field co-ligands such as amine carboxylates. Aquaonly co-ligation appears to exist in the long-known "brownring" [Fe(H 2 O) 5 (NO)] 2 + cation, whichw as preparedo riginally from ferrous salts and NO in sulfuric acid. Ac hloride variant of this species, the green [FeCl 3 (NO)] À ion, was first prepared analoguosly by using hydrochloric instead of sulfuric acid. As at etrahedral species, it is the simple prototypeo fs ulfurbonded {FeNO} 7 (S = 3/2) MNICs of biological significance. Although it has been investigated form ore than ac entury, neitherc lean preparative routes nor reliable structuralp arameters were available for the [FeCl 3 (NO)] À ion and related speciess uch as the [FeCl 2 (NO) 2 ] À ion, ap rototypical dinitrosylirons pecies( a" DNIC"). In this work, both issues have been resolved. In addition, we report on ac omputational study on the ground-and excited-state properties including an assignment of the chromophoric transitions. Photoinduced metastable isomersw ere characterisedi nacombined experimental and computational approacht hat resulted in the confirmation of as ingle photoinduced linkage isomer of the paramagnetic nitrosyl-metal coordination entity.

High‐spin nitrosyl–iron centres of the Enemark–Feltham {FeNO}7 type exist in aqueous solution. Examples include the tentative “brown‐ring” species [Fe(H2O)5(NO)]2+ and a tentative FeII/edta/NO species formed in the processes for scrubbing NO from flue‐gas streams. Inert‐gas bubbling through the solutions subdivides the ferrous nitrosyl complexes in a less stable subclass – a prominent member being the brown‐ring complex – and a more stable subclass to which the edta species belongs. The structural chemistry of the less stable subclass of {FeNO}7‐type complexes from aqueous media is presented here. They contain aminecarboxylato co‐ligands of limited denticity and aqua ligands that complete an OC‐6 environment of the Fe atom. Crystalline compounds for single‐crystal structure analysis were obtained for various co‐ligands: [Fe(H2O)2(ida)(NO)] (2a), [Fe(H2O)(heida)(NO)] (2b), [Fe(H2O)2(NO)(oda)] (2c), [Fe(H2O)2(NO)(phida)]·H2O (2d), [Fe(bnida)(H2O)2(NO)] (2e), [Fe(brbnida)(H2O)2(NO)] (2f) and [Fe(dipic)(H2O)2(NO)] (2g) (ida = iminodiacetate, heida = hydroxyethyliminodiacetate, oda = oxodiacetate, phida = N‐phenyliminodiacetate, bnida = N‐benzyliminodiacetate, brbnida = N‐4‐bromobenzyliminodiacetate, dipic = dipicolinate). The Fe–NO interaction was studied by DFT and CASSCF methods. Due to mostly covalent Fe–NO π bonds, the charge distribution in the less stable subclass is close to FeII(NO) with a small FeIII(NO–) contribution.