roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death

• Published in: Cellular and molecular life sciences : CMLS Vol. 65; no. 4; pp. 644 - 655
• Main Authors: Cohausz, O, Blenn, C, Malanga, M, Althaus, F. R
• Format: Journal Article
• Language: English
• Published: Basel Basel : SP Birkhäuser Verlag Basel 01.02.2008; Birkhäuser-Verlag; Springer Nature B.V
• Subjects: Adenosine diphosphate; AIF; Alkylation; Animals; Apoptosis; Apoptosis - physiology; Apoptosis-inducing factor; Biochemistry; Biomedical and Life Sciences; Biomedicine; caspase; Cell Biology; Cell death; Cell Death - physiology; death; DNA; DNA Damage; Enzymes; enzymology; Fibroblasts; Fibroblasts - enzymology; genetics; HeLa Cells; Humans; Kinetics; Life Sciences; Metabolism; Mice; mitochondria; MNNG; Mortality; PARG; PARP-1; PARP-2; photosynthetically active radiation; physiology; Poly Adenosine Diphosphate Ribose; Poly Adenosine Diphosphate Ribose - metabolism; Poly(ADP-ribose); Poly(ADP-ribose) (PAR); Poly(ADP-ribose) glycohydrolase; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Polymerase Chain Reaction; Research Article; Ribose; RNA interference; RNA, Small Interfering; RNA, Small Interfering - genetics; RNA-mediated interference; Translocation; Poly(ADP-ribose) (PAR); PARG; RNA interference; PARP-2; PARP-1; AIF; MNNG; caspase
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-008-7516-5

Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor (AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and 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 determined 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 induced by an alkylating agent. We found that PARP-1, but not PARP-2 and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was 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.