Electroabsorption (Stark effect) spectra are reported for the charge-transfer transitions of (NH3)SRuL2+ and [(NH3)5R~]2L4+*5+, where L is pyrazine (pz) or 4,4'-bipyridine (4,4'-bpy). The spectra permit experimental estimates of the susceptibility of the transition dipole moment to an electric field, the change in polarizability (TrAu), and the magnitude of the change in permanent electric dipole moment (IApI) associated with many of the metal-to-ligand and metal-to-metal charge-transfer (MLCT and MMCT, respectively) transitions in these complexes. The observed electroabsorption spectra of the MLCT transitions of the monoruthenium complexes are interpreted as arising predominantly from Au and Ap. When L = pz and 4,4'-bpy, the observed values of IApl are (5.3 0.8)lfand (15.8 * 0.2)/fD, respectively, compared with the values of 16.5 and 27.1 D expected for full charge transfer from the metal to the geometric center of the ligand (fis a local electric field correction). Protonation of the monoruthenium complexes has relatively small effects on the observed Au and Ap when L = 4,4'-bpy, but when L = pz, Au appears to change its sign while Ap virtually disappears. A simple electrostatic model qualitatively accounts for the results and indicates that pyrazine allows a much greater degree of delocalization from the ruthenium than 4,4'-bipyridine whose pyridyl rings are probably not coplanar. The electroabsorption spectra of the MLCT region of the biruthenium complexes are very complicated and not quantitatively interpretable on the basis of current information, though interesting and qualitatively suggestive features appear. For the MMCT transitions in the biruthenium mixed-valence complexes where L is pz and 4,4'-bpy, the observed values of lApl are (0.7 * O.l)/fand (28.5 A 1.5)/fD, respectively, compared with the values of 32.7 and 54.3 D expected fur charge transfer in fully localized complexes. These latter results demonstrate that electronic delocalization between the two metals is essentially complete when the bridging ligand is pyrazine, whereas it is significant but incomplete when the bridge is 4,4'-bipyridine. In all complexes, the angle dependence of the electroabsorption demonstrates that Ap and the other field-interactive molecular properties are parallel to the transition dipole moment, as expected if the transition moment lies along the metal-ligand axis. The electroabsorption spectra of all of the monoruthenium and [(NH3)5R~]2L4+ complexes also show evidence for transitions that are weak or obscured in conventional absorption spectra; possible assignments are discussed within the context of a molecular orbital model.

Summary Somatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this novel relationship between transcription, chromatin state and DNA repair, revealing a new, personalized determinant of cancer risk.

in zeolite-Y.I6 [Note pentamethylbenzene with u = 7.15 A passes readily, whereas hexamethylbenzene with u = 7.95 A does not-despite its enhanced donor strength.] Once the arene has penetrated this window, a cavity dimension of -1 3 8, is large enough to accommodate both MV2+ and anthracene (but not tetracene), as depicted in Figure 3. A similar shape selectivity is also observed with zeolite-)< (of related dimensions to zeolite-Y)" but not with the more constricted 4.2 8, aperture in zeolite-A'* or with completely amorphous silica alumina.Owing to the wide structural variations that are allowed by different organic cations, we anticipate that shape selectivity can also be finely tuned in the formation of CT complexes with other types of hydrocarbon donors. W e hope that further tests in progress will provide the requisite information for the detailed mapping of substrate access to various zeolite structures,19 especially with regard to both their kinetic and thermodynamic properties in the liquid phase.Acknowledgment. W e thank T. M. Bockman for helpful discussions, J. D. Korp for crystallographic assistance, and the National Science Foundation and Robert A. Welch Foundation for financial support. : Tables of data collection and processing parameters, atomic coordinates and isotropic displacement parameters, bond lengths and angles, and anisotropic displacement parameters (4 pages). Ordering information is given on any current masthead page. (14) Zehnder, M.; Belser, P.; von Zelewsky, A. Acta. Crystallogr., Sect. A 1981, 37, C239, 108. (15) (a) Juris, A,; Barigelletti, F.; Balzani, V.; Belser, P.; von Zelewsky, A. Isr. J. Chem. 1982, 22, 87-90. (b) Barigelletti. F.; Juris. A,; Balzani. V.; Belser, P.; von Zelewsky, A. Supplementary Material Available

The phosphorylation of H2Ax on its S139 site, γH2Ax, is important during DNA double-strand repair and is considered necessary for assembly of repair complexes, but its functional role after other kinds of DNA damage is less clear. We have measured the survival of isogenic mouse cell lines with the H2Ax gene knocked out, and replaced with wild-type or mutant (S139A) H2Ax genes, exposed to a range of agents with varied mechanisms of DNA damage. Knockout and mutant cells were sensitive to γ-rays, etoposide, temozolamide, and endogenously generated reactive oxygen species, each of which can include double-strand breaks among their spectra of DNA lesions. The absence or mutation of H2Ax had no influence on sensitivity to cisplatin or mitomycin C. Although UV light induced the highest levels of γH2Ax, mutation of S139 had no influence on UV sensitivity or the UV DNA damage response. Complete loss of H2Ax reduced the survival of cells exposed to UV light and reduced pChk1 induction, suggesting that sites other than S139 may impact the ATR-pChk1 pathway. The relative intensity of γH2Ax measured in Western blots in wild-type cells did not correlate with the functional importance of γH2Ax. The use of γH2Ax as a general biomarker of DNA damage is therefore potentially misleading because it is not an unambiguous indicator of double-strand breaks, and a significant fraction of DNA repair, especially involving nucleotide excision or crosslink repair, can occur without functional involvement of γH2Ax.alkylation | rotenone | caffeine | poly(ADP-ribose) polymerase | veliparib