Inhibition of simian virus 40 DNA replication in vitro by poly(ADP-ribosyl)ated diadenosine tetraphosphate.
Poly(ADP-ribosyl)ated diadenosine tetraphosphate was found to inhibit the in vitro replication of SV40 DNA. This inhibition was sensitive to preincubation of the polymer with either poly(ADP-ribose) glycohydrolase, diadenosine tetraphosphate (Ap4A):ADP phosphohydrolase, or an excess of free Ap4A. In contrast, the general catalytic activity of DNA polymerase was not inhibited by the poly(ADP-ribosyl)ated Ap4A when activated salmon sperm DNA was used as a template. These data suggest that inhibition of SV40 DNA replication by poly(ADP-ribosyl)ated Ap4A requires both the intact polymer and intact Ap4A moiety and is specific to events occurring during the initiation or elongation of a double-stranded template. Since both poly(ADP-ribose) and Ap4A accumulate in cultured mammalian cells following stresses which are accompanied by DNA strand breaks, these data are consistent with a model in which poly(ADP-ribosyl)ated Ap4A inhibits DNA replication following DNA damage.
Baker
J C
JC
Department of Biochemistry, University of California, Berkeley 94720.
Smale
S T
ST
Tjian
R
R
Ames
B N
BN
D000227:Adenine Nucleotides / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D015226:Dinucleoside Phosphates; D009702:Nucleoside Diphosphate Sugars / Q000494:pharmacology*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism / Q000494:pharmacology*; D013539:Simian virus 40 / Q000187:drug effects / Q000235:genetics*
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D009702:Nucleoside Diphosphate Sugars; D011064:Poly Adenosine Diphosphate Ribose; C020733:diadenosine tetraphosphate; D004259:DNA-Directed DNA Polymerase