Interaction of poly(ADP-ribose)polymerase with DNA polymerase alpha.

Homogeneously purified poly(ADP-ribose) polymerase (PARP) specifically stimulated the activity of immunoaffinity-purified calf or human DNA polymerase alpha by about 6 to 60-fold. Apparently, poly(ADP-ribosyl)ation of DNA polymerase alpha was not necessary for the stimulation. The effects of PARP on DNA polymerase alpha were biphasic: at very low concentrations of DNA, it rather inhibited its activity, whereas, at higher DNA concentrations, PARP greatly stimulated it. The autopoly(ADP-ribosyl)ation of PARP suppressed both its stimulatory and inhibitory effects. By immunoprecipitation with an anti-DNA polymerase alpha antibody, it was clearly shown that PARP may be physically associated with DNA polymerase alpha. Stimulation of DNA polymerase alpha may be attributed to the physical association between the two, rather than to the DNA-binding capacity of PARP, since the PARP fragment containing only the DNA binding domain showed little stimulatory activity. The existence of PARP-DNA polymerase alpha complexes were also detected in crude extracts of calf thymus.