Learn More
PrP(C)-deficient mice expressing prion protein variants with large amino-proximal deletions (termed PrP(DeltaF)) suffer from neurodegeneration, which is rescued by full-length PrP(C). We now report that expression of PrP(DeltaCD), a PrP variant lacking 40 central residues (94-134), induces a rapidly progressive, lethal phenotype with extensive central and(More)
In the present paper, the involvement of the family of poly(ADP-ribose) polymerases (PARPs), and especially of PARP-1, in mammalian longevity is reviewed. PARPs catalyse poly(ADP-ribosyl)ation, a covalent post-translational protein modification in eukaryotic cells. PARP-1 and PARP-2 are activated by DNA strand breaks, play a role in DNA base-excision repair(More)
DNA strand breaks induced by alkylating agents, oxidants, or ionizing radiation trigger the covalent modification of nuclear proteins with poly(ADP-ribose), which is catalyzed for the most part by poly(ADP-ribose) polymerase-1 and plays a role in DNA base-excision repair. Poly(ADP-ribosyl)ation capacity of mononuclear blood cells correlates positively with(More)
The cellular prion protein (PrP(C)) is a GPI-anchored cell-surface protein. A small subset of PrP(C) molecules, however, can be integrated into the ER-membrane via a transmembrane domain (TM), which also harbors the most highly conserved regions of PrP(C), termed the hydrophobic core (HC). A mutation in HC is associated with prion disease resulting in an(More)
Poly(ADP-ribosyl)ation, which is the posttranslational modification of proteins with poly(ADP-ribose), is catalysed by poly(ADP-ribose) polymerases. DNA-strand break induced catalytic activation of two PARP isoforms, namely PARP-1 and -2, are in involved in DNA base-excision repair and other repair pathways. A body of correlative data suggests a link(More)
Cellular DNA repair activities can be expected to control the rate of the ageing process by keeping the steady-state levels of DNA damage, which is continuously induced by endogenous and exogenous damaging agents, at low levels. Poly(ADP-ribosyl)ation is one of the immediate biochemical reactions of eukaryotic cells to DNA damage and is functionally(More)
  • 1