Acetylation of DNA Polymerase Beta Regulates the Choice of the Base Excision Repair Pathway

poster abstractBase excision repair (BER) is the main pathway through which base damages are repaired in the cell. Single nucleotide damage can be corrected either through short patch BER (SP-BER), in which the single damaged base is replaced, or long patch BER (LP-BER), in which two or more nucleotides can be replaced. Several proteins are involved in the process including DNA polymerase beta (pol β) and FEN1, both of which are the focus for this study. DNA pol β is a multifunctional protein which contains both polymerase and lyase properties. In LP-BER, pol β displaces the uncleaved 5’dRP moiety into a flap structure which is recognized and cleaved by FEN1 and subsequently ligated by DNA ligase 1. Previous in vitro studies show that pol β acetylation reduces lyase activity, requiring repair to proceed via LP-BER. In this study, we determined the effect of in vitro acetylation on the enzymatic activities of DNA pol β and FEN1. Both unmodified and acetylated forms of pol β were tested for their synthesis and strand displacement activities. Interestingly, acetylated forms of pol β showed much greater activity at all concentrations versus unmodified forms. Interestingly we also found that FEN1 cleavage activity was increased in reactions containing acetylated pol β compared to the unmodified form due to the increased strand displacement activity of the polymerase. Our results suggest that the acetylated form of DNA pol β more actively participates in LP-BER, creating longer strands of corrected, higher fidelity nucleotides

Impurity-Induced Bound Excitations on the Surface of Bi2Sr2CaCu2O8

We have probed the effects of atomic-scale impurities on superconductivity in Bi_{2}Sr_{2}CaCu_{2}O_{8} by performing low-temperature tunneling spectroscopy measurements with a scanning tunneling microscope. Our results show that non-magnetic defect structures at the surface create localized low-energy excitations in their immediate vicinity. The impurity-induced excitations occur over a range of energies including the middle of the superconducting gap, at the Fermi level. Such a zero bias state is a predicted feature for strong non-magnetic scattering in a d-wave superconductor.Comment: 4 pages, revtex, 4 figures. To appear in Physical Review Letter

Performing at extreme altitude: muscle cellular and subcellular adaptations

This review reports on the collaborative efforts of the Department of Physiology of the University of Geneva headed by Paolo Cerretelli, the Research Institute at the Federal School of Physical Education in Magglingen and the Department of Anatomy of the University of Bern to elucidate the functional and structural conditions for and consequences of climbing successfully at altitudes in excess of 8000m. Using a combination of physiological whole body measurements with biochemical, histochemical and morphometric analyses of muscle biopsy samples we were able to establish specific phenotypical alterations of muscle tissue exposed to extreme hypoxia and stress for prolonged periods of time. The decline in aerobic work capacity could be shown to be a consequence of a loss of muscle mass as well as of muscle tissue oxidative capacity whereby muscle capillarity was found to be maintained. The degradation of muscle tissue was further characterized by an increase in muscle lipofuscin. The latter is believed to be the consequence of lipid peroxidation eventually related to mitochondrial loss. Current work ensuing from our long-term collaboration suggests that Sherpas might be protected against the damaging effect of hypoxia by antioxidant mechanisms protecting their muscles under the conditions of extreme altitud