12 Pages

The Life History of Poly(ADP-ribose)

WithMiyoko Ikejima, Yosuke Sawada, An Quoc Dang, Robert J. Suhadolnik, D. Michael Gill

We present arguments and data in support of the following sequence of events in ghost cells. 1) Poly(ADP-ribose, ADPR) synthetase, activated by binding to DNA at a break or other anomaly, synthesizes chains of polymer upon itself, adding new residues at the proximal 1″ terminus of the growing chain. 2) Free chains of poly(ADPR) are produced by release from the active site or by internal glycohydrolysis of the growing chains without hindering the continued elongation. Subsequent glycohydrolysis cuts the free chains down to monomers. 3) ADP-ribosylation of core histones may involve soluble intermediates of some form. Glycohydrolysis generates a limit digest with only short histone-bound chains. 4) Most ADP-ribosylation of histone HI occurs by the addition of single free ADPR residues independently of poly(ADPR) synthetase.