Group Althaus

Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor (AIF). PAR is involved in the translocation of AIF from mitochondria to the nucleus where it triggers cell death. In living cells, PAR molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we determine the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose)glycohydrolase (PARG), the key enzymes configuring PAR molecules, in cell death. We found that PARP-1, but not PARP-2 and PARG, contribute to alkylation-induced cell death. Likewise, AIF translocation is only affected by PARP-1. PARP-1 seems to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved. - A different involvement is observed in oxidative stress. PARG is a major editor of the signal for AIF-translocation and cell death. We are currently exploring the mechanistic details of these phenomena.