Trans-dominant inhibition of poly(ADP-ribosyl)ation potentiates carcinogen induced gene amplification in SV40-transformed Chinese hamster cells.
Poly(ADP-ribose) polymerase (PARP) is an evolutionally conserved nuclear protein present in most eukaryotic species and catalyzes the formation of ADP-ribose polymers covalently attached to proteins. PARP is strongly activated by DNA single- or double-strand breaks and is thought to be involved in cellular responses to DNA damage. Based on the SV40-transformed Chinese hamster cell line CO60, we had established stable transfectants that overexpress the PARP DNA-binding domain conditionally. DNA-binding domain overexpression led to trans-dominant inhibition of poly(ADP-ribosyl)ation and sensitized the cells to genotoxic agents. Using the amplification of chromosomally integrated SV40 DNA as an indicator system, we show here that trans-dominant PARP inhibition potentiates genetic instability induced by N-methyl-N'-nitro-N-nitrosoguanidine treatment of cells.
Kupper
J H
JH
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Heidelberg, Germany.
Müller
M
M
Bürkle
A
A
D000818:Animals; D016466:CHO Cells; D002273:Carcinogens / Q000494:pharmacology; D002461:Cell Line, Transformed; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D005784:Gene Amplification; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D013539:Simian virus 40; D014162:Transfection
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases